Impact of OCT4 and Its Related Signaling Pathways on Gastrointestinal Cancers: Focusing on Targeted Therapy
Abstract
There are many pieces of evidence support the effect of cancer stem cells on the initiation and progression of cancer. However, related mechanisms involved in these phenomena are far more complicated to understand. The function of different stemness factorsin cancer stem cells (CSCs) and their complex associations at different levels of cancer have been reported. Therefore, it seems that focusing on one master factor would be more helpful to complete the puzzle of singling pathways in these cells. Octamer-binding transcription factor 4 (OCT4) also known as POU domain, class 5, transcription factor 1(POU5F1), one of these key pluripotency factors, has important roles in both embryogenesis and tumorigenesis.
In this review, we gathered information about the association of different markers with OCT4 expression in three types of gastrointestinal cancers including esophageal, gastric and colorectal cancers.
OCT4 through different signaling pathways has an impact on different processes of gastrointestinal cancers such as proliferation, invasion, and metastasis.
Based on the literature, OCT4 has great effects on cancer progression at different stages, therefore we suggested it has potential implications in therapeutic options.
1. Zou GM. Cancer initiating cells or cancer stem cells in the gastrointestinal tract and liver. Journal of cellular physiology. 2008;217(3):598-604.
2. Zhu R, Yang Y, Tian Y, Bai J, Zhang X, Li X, et al. Ascl2 knockdown results in tumor growth arrest by miRNA-302b-related inhibition of colon cancer progenitor cells. PloS one. 2012;7(2):e32170.
3. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. cell. 2007;131(5):861-72.
4. Rassouli FB, Matin MM, Bahrami AR, Ghaffarzadegan K, Cheshomi H, Lari S, et al. Evaluating stem and cancerous biomarkers in CD15+ CD44+ KYSE30 cells. Tumor Biology. 2013;34(5):2909-20.
5. Mueller M, Hermann PC, Liebau S, Weidgang C, Seufferlein T, Kleger A, et al. The role of pluripotency factors to drive stemness in gastrointestinal cancer. Stem cell research. 2016;16(2):349-57.
6. Lu X, Mazur SJ, Lin T, Appella E, Xu Y. The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis. Oncogene. 2014;33(20):2655.
7. Bornschein J, Tóth K, Selgrad M, Kuester D, Wex T, Molnár B, et al. Dysregulation of CDX1, CDX2 and SOX2 in patients with gastric cancer also affects the non-malignant mucosa. Journal of clinical pathology. 2013;66(9):819-22.
8. Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature. 2013;501(7467):355.
9. Lu Y, Futtner C, Rock JR, Xu X, Whitworth W, Hogan BL, et al. Evidence that SOX2 overexpression is oncogenic in the lung. PloS one. 2010;5(6):e11022.
10. Tsukamoto T, Mizoshita T, Mihara M, Tanaka H, Takenaka Y, Yamamura Y, et al. Sox2 expression in human stomach adenocarcinomas with gastric and gastric‐and‐intestinal‐mixed phenotypes. Histopathology. 2005;46(6):649-58.
11. Amsterdam A, Raanan C, Schreiber L, Freyhan O, Fabrikant Y, Melzer E, et al. Differential localization of LGR5 and Nanog in clusters of colon cancer stem cells. Acta histochemica. 2013;115(4):320-9.
12. Raghoebir L, Bakker ER, Mills JC, et al. SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype. Journal of molecular cell biology. 2012;4(6):377-85.
13. Chen S, Xu Y, Chen Y, Li X, Mou W, Wang L, et al. SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells. PloS one. 2012;7(5):e36326.
14. Ibrahim EE, Babaei‐Jadidi R, Saadeddin A, Spencer‐Dene B, Hossaini S, Abuzinadah M, et al. Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1‐and TCF‐dependent mechanisms. Stem cells. 2012;30(10):2076-87.
15. Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Müller F, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC cancer. 2011;11(1):42.
16. Yasuda H, Tanaka K, Okita Y, Araki T, Saigusa S, Toiyama Y, et al. CD133, OCT4, and NANOG in ulcerative colitis-associated colorectal cancer. Oncology letters. 2011;2(6):1065-71.
17. Shirzadeh E, Najafi M, Nazarzadeh M, Fazli G, Falanji F, Aldaghi LS, et al. Expression of Pluripotency markers, SOX2 and OCT4, in pterygium development. Critical Reviews™ in Eukaryotic Gene Expression. 2018;28(2).
18. Amini S, Fathi F, Mobalegi J, Sofimajidpour H, Ghadimi T. The expressions of stem cell markers: Oct4, Nanog, Sox2, nucleostemin, Bmi, Zfx, Tcl1, Tbx3, Dppa4, and Esrrb in bladder, colon, and prostate cancer, and certain cancer cell lines. Anatomy & cell biology. 2014;47(1):1-11.
19. Zhang G, Ma L, Xie Y-K, Miao X-B, Jin C. Esophageal cancer tumorspheres involve cancer stem-like populations with elevated aldehyde dehydrogenase enzymatic activity. Molecular medicine reports. 2012;6(3):519-24.
20. Santagata S, Ligon KL, Hornick JL. Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. The American journal of surgical pathology. 2007;31(6):836-45.
21. Cheng L. Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer. 2004;101(9):2006-10.
22. Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Annals of surgical oncology. 2009;16(12):3488-98.
23. Kim R-J, Nam J-S. OCT4 expression enhances features of cancer stem cells in a mouse model of breast cancer. Laboratory animal research. 2011;27(2):147-52.
24. Chen J, Pan Y, He B, Ying H, Wang F, Sun H, et al. Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells. International journal of oncology. 2015;47(4):1476-84.
25. Schöler HR. Octamania: the POU factors in murine development. Trends in genetics: TIG. 1991;7(10):323-9.
26. Brehm A, Ohbo K, Schöler H. The carboxy-terminal transactivation domain of Oct-4 acquires cell specificity through the POU domain. Molecular and cellular biology. 1997;17(1):154-62.
27. Pan GJ, Chang ZY, Schöler HR, Duanqing P. Stem cell pluripotency and transcription factor Oct4. Cell research. 2002;12(5-6):321.
28. Schöler H, Dressler GR, Balling R, Rohdewohld H, Gruss P. Oct‐4: a germline‐specific transcription factor mapping to the mouse t‐complex. The EMBO journal. 1990;9(7):2185-95.
29. Pesce M, Schöler HR. Oct‐4: gatekeeper in the beginnings of mammalian development. Stem cells. 2001;19(4):271-8.
30. Deb-Rinker P, Ly D, Jezierski A, Sikorska M, Walker PR. Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation. Journal of Biological Chemistry. 2005;280(8):6257-60.
31. Niwa H. Molecular mechanism to maintain stem cell renewal of ES cells. Cell structure and function. 2001;26(3):137-48.
32. Niwa H, Miyazaki J-i, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature genetics. 2000;24(4):372.
33. Tai M-H, Chang C-C, Olson LK, Trosko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26(2):495-502.
34. Gidekel S, Pizov G, Bergman Y, Pikarsky E. Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer cell. 2003;4(5):361-70.
35. Monk M, Holding C. Human embryonic genes re-expressed in cancer cells. Oncogene. 2001;20(56):8085.
36. LöNNROTH C, ANDeRSSON M, Asting AG, Nordgren S, Lundholm K. Preoperative low dose NSAID treatment influences the genes for stemness, growth, invasion and metastasis in colorectal cancer. International journal of oncology. 2014;45(6):2208-20.
37. Wang X, Dai J. Concise review: isoforms of OCT4 contribute to the confusing diversity in stem cell biology. Stem cells. 2010;28(5):885-93.
38. Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW. OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem cells. 2008;26(12):3068-74.
39. Costabile V, Duraturo F, Delrio P, Rega D, Pace U, Liccardo R, et al. Lithium chloride induces mesenchymal‑to‑epithelial reverting transition in primary colon cancer cell cultures. international journal of oncology. 2015;46(5):1913-23.
40. Chen Z, Xu WR, Qian H, Zhu W, Bu XF, Wang S, et al. Oct4, a novel marker for human gastric cancer. Journal of surgical oncology. 2009;99(7):414-9.
41. Cauffman G, Liebaers I, Van Steirteghem A, Van de Velde H. POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos. Stem cells. 2006;24(12):2685-91.
42. Lee J, Kim HK, Rho J-Y, Han Y-M, Kim J. The human OCT-4 isoforms differ in their ability to confer self-renewal. Journal of Biological Chemistry. 2006.
43. Grandér D, Johnsson P. Pseudogene-expressed RNAs: emerging roles in gene regulation and disease. Long Non-coding RNAs in Human Disease: Springer; 2015. p. 111-26.
44. An Y, Furber KL, Ji S. Pseudogenes regulate parental gene expression via ce RNA network. Journal of cellular and molecular medicine. 2017;21(1):185-92.
45. Pain D, Chirn G-W, Strassel C, Kemp DM. Multiple retropseudogenes from pluripotent cell-specific gene expression indicates a potential signature for novel gene identification. Journal of Biological Chemistry. 2005;280(8):6265-8.
46. Suo G, Han J, Wang X, Zhang J, Zhao Y, Zhao Y, et al. Oct4 pseudogenes are transcribed in cancers. Biochemical and biophysical research communications. 2005;337(4):1047-51.
47. Villodre ES, Kipper FC, Pereira MB, Lenz G. Roles of OCT4 in tumorigenesis, cancer therapy resistance and prognosis. Cancer treatment reviews. 2016;51:1-9.
48. Poursani EM, Soltani BM, Mowla SJ. Differential expression of OCT4 pseudogenes in pluripotent and tumor cell lines. Cell Journal (Yakhteh). 2016;18(1):28.
49. Poursani EM, Mehravar M, Soltani BM, Mowla SJ. Novel variant of OCT4B4 is differentially expressed in human embryonic stem and embryonic carcinoma cells. Gene. 2017;627:369-72.
50. Xu G, Yang L, Zhang W, Wei X. All the tested human somatic cells express both Oct4A and its pseudogenes but express Oct4A at much lower levels compared with its pseudogenes and human embryonic stem cells. Stem cells and development. 2015;24(13):1546-57.
51. Guo X, Tang Y. OCT4 pseudogenes present in human leukemia cells. Clinical and experimental medicine. 2012;12(4):207-16.
52. Wang L, Guo Z-Y, Zhang R, Xin B, Chen R, Zhao J, et al. Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma. Carcinogenesis. 2013;34(8):1773-81.
53. Napier KJ, Scheerer M, Misra S. Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities. World journal of gastrointestinal oncology. 2014;6(5):112.
54. Thrift AP. The epidemic of oesophageal carcinoma: where are we now? Cancer epidemiology. 2016;41:88-95.
55. Cantz T, Key G, Bleidiβel M, Gentile L, Han DW, Brenne A, et al. Absence of OCT4 expression in somatic tumor cell lines. Stem cells. 2008;26(3):692-7.
56. Zhou X, Huang G-R, Hu P. Over-expression of Oct4 in human esophageal squamous cell carcinoma. Molecules and cells. 2011;32(1):39-45.
57. He W, Wang Z, Wang Q, Fan Q, Shou C, Wang J, et al. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis. BMC cancer. 2009;9(1):426.
58. Nagaraja V, Eslick GD. Forthcoming prognostic markers for esophageal cancer: a systematic review and meta-analysis. Journal of gastrointestinal oncology. 2014;5(1):67.
59. Li C, Yan Y, Ji W, Bao L, Qian H, Chen L, et al. OCT4 positively regulates Survivin expression to promote cancer cell proliferation and leads to poor prognosis in esophageal squamous cell carcinoma. PloS one. 2012;7(11):e49693.
60. Li Z, Li X, Li C, Su Y, Fang W, Zhong C, et al. Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma. Cancer letters. 2014;354(1):77-86.
61. Li C, Zhu M, Lou X, Liu C, Chen H, Lin X, et al. Transcriptional factor OCT4 promotes esophageal cancer metastasis by inducing epithelial-mesenchymal transition through VEGF-C/VEGFR-3 signaling pathway. Oncotarget. 2017;8(42):71933.
62. Izadpanah MH, Abbaszadegan MR, Fahim Y, Forghanifard MM. Ectopic expression of TWIST1 upregulates the stemness marker OCT4 in the esophageal squamous cell carcinoma cell line KYSE30. Cellular & molecular biology letters. 2017;22(1):33.
63. Vaiphei K, Sinha SK, Kochhar R. Comparative analysis of Oct4 in different histological subtypes of esophageal squamous cell carcinomas in different clinical conditions. Asian Pac J Cancer Prev. 2014;15(8):3519-24.
64. Stock M, Otto F. Gene deregulation in gastric cancer. Gene. 2005;360(1):1-19.
65. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer management and research. 2018;10:239.
66. Rassouli FB, Matin MM, Bahrami AR, Ghaffarzadegan K, Sisakhtnezhad S, Cheshomi H, et al. SOX2 expression in gastrointestinal cancers of Iranian patients. The International journal of biological markers. 2015;30(3):315-20.
67. Yang L, Ping Y-F, Yu X, Qian F, Guo Z-J, Qian C, et al. Gastric cancer stem-like cells possess higher capability of invasion and metastasis in association with a mesenchymal transition phenotype. Cancer letters. 2011;310(1):46-52.
68. Fukuda K, Saikawa Y, Ohashi M, Kumagai K, Kitajima M, Okano H, et al. Tumor initiating potential of side population cells in human gastric cancer. International journal of oncology. 2009;34(5):1201-7.
69. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem cells. 2009;27(5):1006-20.
70. Liu J, Ma L, Xu J, Liu C, Zhang J, Liu J, et al. Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties. International journal of oncology. 2013;42(2):453-9.
71. Zhang X, Hua R, Wang X, Huang M, Gan L, Wu Z, et al. Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer. Oncotarget. 2016;7(9):9815.
72. Nosrati A, Naghshvar F, Khanari S. Cancer stem cell markers CD44, CD133 in primary gastric adenocarcinoma. International journal of molecular and cellular medicine. 2014;3(4):279.
73. Qiao XT, Gumucio DL. Current molecular markers for gastric progenitor cells and gastric cancer stem cells. Journal of gastroenterology. 2011;46(7):855-65.
74. Hong KJ, Wu DC, Cheng KH, Chen LT, Hung WC. RECK Inhibits Stemness Gene Expression and Tumorigenicity of Gastric Cancer Cells by Suppressing ADAM‐M ediated Notch1 Activation. Journal of cellular physiology. 2014;229(2):191-201.
75. Mao J, Liang Z, Zhang B, Yang H, Li X, Fu H, et al. UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell‐Exosome Promoted Gastric Cancer Progression via Wnt/β‐Catenin Pathway. Stem Cells. 2017;35(11):2267-79.
76. Mao J, Fan S, Ma W, Fan P, Wang B, Zhang J, et al. Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell death & disease. 2015;5(1):e1039.
77. Wang S, Liu F, Deng J, Cai X, Han J, Liu Q. Long noncoding RNA ROR regulates proliferation, invasion, and stemness of gastric cancer stem cell. Cellular Reprogramming (Formerly" Cloning and Stem Cells"). 2016;18(5):319-26.
78. Li N, Deng W, Ma J, Wei B, Guo K, Shen W, et al. Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Medical oncology. 2015;32(1):433.
79. Ji W, Jiang Z. Effect of shRNA‑mediated inhibition of Nanog gene expression on the behavior of human gastric cancer cells. Oncology letters. 2013;6(2):367-74.
80. Zhan Y-y, He J-p, Chen H-z, Wang W-j, Cai J-c. Orphan receptor TR3 is essential for the maintenance of stem-like properties in gastric cancer cells. Cancer letters. 2013;329(1):37-44.
81. Nishii T, Yashiro M, Shinto O, Sawada T, Ohira M, Hirakawa K. Cancer stem cell‐like SP cells have a high adhesion ability to the peritoneum in gastric carcinoma. Cancer science. 2009;100(8):1397-402.
82. Lin T, Ding Y-Q, Li J-M. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Medical oncology. 2012;29(2):878-85.
83. Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. International journal of cancer. 2011;128(11):2645-52.
84. Hayashi H, Arao T, Togashi Y, Kato H, Fujita Y, De Velasco M, et al. The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. Oncogene. 2015;34(2):199.
85. Chen B, Zhu Z, Li L, Ye W, Zeng J, Gao J, et al. Effect of overexpression of Oct4 and Sox2 genes on the biological and oncological characteristics of gastric cancer cells. OncoTargets and therapy. 2019;12:4667.
86. Kong D, Su G, Zha L, Zhang H, Xiang J, Xu W, et al. Coexpression of HMGA2 and Oct4 predicts an unfavorable prognosis in human gastric cancer. Medical oncology. 2014;31(8):130.
87. Guo J, Wang B, Fu Z, Wei J, Lu W. Hypoxic microenvironment induces EMT and upgrades stem-like properties of gastric cancer cells. Technology in cancer research & treatment. 2016;15(1):60-8.
88. Chen X-L, Chen X-Z, Wang Y-G, He D, Lu Z-H, Liu K, et al. Clinical significance of putative markers of cancer stem cells in gastric cancer: A retrospective cohort study. Oncotarget. 2016;7(38):62049.
89. Wang X-F, Zhang X-W, Hua R-X, Du Y-Q, Huang M-Z, Liu Y, et al. Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer. Oncotarget. 2016;7(39):63352.
90. Zhou G-X, Li X-Y, Zhang Q, Zhao K, Zhang C-P, Xue C-H, et al. Effects of the hippo signaling pathway in human gastric cancer. Asian Pacific journal of cancer prevention. 2013;14(9):5199-205.
91. Zhang Y, Zhang X, Wang X, Gan L, Yu G, Chen Y, et al. Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinal-type gastric cancer tumorigenicity through the downregulation of Oct4. Cancer letters. 2012;321(1):45-54.
92. Al-Marzoqee FY, Khoder G, Al-Awadhi H, John R, Beg A, Vincze A, et al. Upregulation and inhibition of the nuclear translocation of Oct4 during multistep gastric carcinogenesis. International journal of oncology. 2012;41(5):1733-43.
93. Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi REM, Corcione F. Worldwide burden of colorectal cancer: a review. Updates in surgery. 2016;68(1):7-11.
94. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106.
95. Dalerba P, Dylla SJ, Park I-K, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proceedings of the National Academy of Sciences. 2007;104(24):10158-63.
96. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111.
97. Zeuner A, Todaro M, Stassi G, De Maria R. Colorectal cancer stem cells: from the crypt to the clinic. Cell stem cell. 2014;15(6):692-705.
98. Liu Y-H, Li Y, Liu X-H, Sui H-M, Liu Y-X, Xiao Z-Q, et al. A signature for induced pluripotent stem cell–associated genes in colorectal cancer. Medical Oncology. 2013;30(1):426.
99. Dewi DL, Ishii H, Haraguchi N, Nishikawa S, Kano Y, Fukusumi T, et al. Dicer 1, ribonuclease type III modulates a reprogramming effect in colorectal cancer cells. International journal of molecular medicine. 2012;29(6):1060-4.
100. Chen S, Song X, Chen Z, Li X, Li M, Liu H, et al. CD133 expression and the prognosis of colorectal cancer: a systematic review and meta-analysis. PloS one. 2013;8(2):e56380.
101. Sedlar IT, Petricevic J, Saraga-Babic M, Pintaric I, Vukojevic K. Apoptotic pathways and stemness in the colorectal epithelium and lamina propria mucosae during the human embryogenesis and carcinogenesis. Acta histochemica. 2016;118(7):693-703.
102. Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell stem cell. 2014;14(3):342-56.
103. Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem cells. 2012;30(11):2378-86.
104. Jung P, Sato T, Merlos-Suárez A, Barriga FM, Iglesias M, Rossell D, et al. Isolation and in vitro expansion of human colonic stem cells. Nature medicine. 2011;17(10):1225.
105. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer research. 2009;69(8):3382-9.
106. Koshkin S, Danilova A, Raskin G, Petrov N, Bajenova O, O’Brien SJ, et al. Primary cultures of human colon cancer as a model to study cancer stem cells. Tumor Biology. 2016;37(9):12833-42.
107. Saiki Y, Ishimaru S, Mimori K, Takatsuno Y, Nagahara M, Ishii H, et al. Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Annals of surgical oncology. 2009;16(9):2638-44.
108. Shi Z, Bai R, Fu Z-x, Zhu Y-l, Wang R-f, Zheng S. Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells. Journal of Zhejiang University SCIENCE B. 2012;13(1):11-9.
109. Liu R-l, Zhang Z-h, Zhao W-m, Meng W, Qi S-y, Jing L, et al. Expression of nucleostemin in prostate cancer and its effect on the proliferation of PC-3 cells. Chinese medical journal. 2008;121(4):299-304.
110. Motzer RJ, Escudier B, Oudard S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma. Cancer. 2010;116(18):4256-65.
111. Munro MJ, Wickremesekera SK, Peng L, Marsh RW, Itinteang T, Tan ST. Cancer stem cell subpopulations in primary colon adenocarcinoma. PloS one. 2019;14(9):e0221963.
112. Koren A, Rijavec M, Kern I, Sodja E, Korosec P, Cufer T. BMI1, ALDH1A1, and CD133 transcripts connect epithelial-mesenchymal transition to cancer stem cells in lung carcinoma. Stem cells international. 2016;2016.
113. Litwin M, Dubis J, ARCZYŃSKA K, Piotrowska A, Frydlewicz A, Karczewski M, et al. Correlation of HIWI and HILI expression with cancer stem cell markers in colorectal cancer. Anticancer research. 2015;35(6):3317-24.
114. Ghodsi M, Jafarian AH, Montazer M, Sadeghian MH, Forghanifard MM. Diagnostic clinical relevance of developmental pluripotency-associated 2 (DPPA2) in colorectal cancer. International Journal of Surgery. 2015;13:193-7.
115. Padín-Iruegas M-E, Herranz-Carnero M, Aguin-Losada S, Brozos-Vazquez E, Anido-Herranz U, Antunez-Lopez J-R, et al. Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer. Oncology reports. 2013;29(6):2467-72.
116. Lemos C, Hardt MS, Juneja M, Voss C, Förster S, Jerchow B, et al. MACC1 induces tumor progression in transgenic mice and colorectal cancer patients via increased pluripotency markers Nanog and Oct4. Clinical Cancer Research. 2016.
117. Fidalgo M, Faiola F, Pereira C-F, Ding J, Saunders A, Gingold J, et al. Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. Proceedings of the National Academy of Sciences. 2012;109(40):16202-7.
118. Wang ZX, Teh CHL, Chan CMY, et al. The transcription factor Zfp281 controls embryonic stem cell pluripotency by direct activation and repression of target genes. Stem Cells. 2008;26(11):2791-9.
119. Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, et al. A protein interaction network for pluripotency of embryonic stem cells. nature. 2006;444(7117):364.
120. Takeuchi A, Mishina Y, Miyaishi O, Kojima E, Hasegawa T, Isobe K-i. Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells during mouse embryogenesis. Nature genetics. 2003;33(2):172.
121. Chang C-J, Chien Y, Lu K-H, Chang S-C, Chou Y-C, Huang C-S, et al. Oct4-related cytokine effects regulate tumorigenic properties of colorectal cancer cells. Biochemical and biophysical research communications. 2011;415(2):245-51.
122. Gazouli M, Roubelakis MG, Theodoropoulos GE, Papailiou J, Vaiopoulou A, Pappa KI, et al. OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer. Molecular carcinogenesis. 2012;51(2):165-73.
123. Dai X, Ge J, Wang X, Qian X, Zhang C, Li X. OCT4 regulates epithelial-mesenchymal transition and its knockdown inhibits colorectal cancer cell migration and invasion. Oncology reports. 2013;29(1):155-60.
124. Wang R, Bhattacharya R, Ye X, Fan F, Boulbes DR, Xia L, et al. Endothelial cells activate the cancer stem cell‐associated NANOGP8 pathway in colorectal cancer cells in a paracrine fashion. Molecular oncology. 2017;11(8):1023-34.
125. Williamson JM, Thairu N, Katsoulas N, Stamp G, Ahmad R, du Potet E, et al. Impact of portal vein embolization on expression of cancer stem cell markers in regenerated liver and colorectal liver metastases. Scandinavian journal of gastroenterology. 2010;45(12):1472-9.
126. Miranda PV, Allaire A, Sosnik J, Visconti PE. Localization of low-density detergent-resistant membrane proteins in intact and acrosome-reacted mouse sperm. Biology of reproduction. 2009;80(5):897-904.
127. Batsaikhan B-E, Yoshikawa K, Kurita N, Iwata T, Takasu C, Kashihara H, et al. Cyclopamine decreased the expression of sonic hedgehog and its downstream genes in colon cancer stem cells. Anticancer research. 2014;34(11):6339-44.
128. Liang K, Zhou G, Zhang Q, Li J, Zhang C. Expression of hippo pathway in colorectal cancer. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association. 2014;20(3):188.
129. Wen K, Fu Z, Wu X, Feng J, Chen W, Qian J. Oct-4 is required for an antiapoptotic behavior of chemoresistant colorectal cancer cells enriched for cancer stem cells: effects associated with STAT3/Survivin. Cancer letters. 2013;333(1):56-65.
130. Khorrami S, Hosseini AZ, Mowla SJ, Malekzadeh R. Verification of ALDH activity as a biomarker in colon cancer stem cells-derived HT-29 cell line. Iranian journal of cancer prevention. 2015;8(5).
131. Voutsadakis IA. Pluripotency transcription factors in the pathogenesis of colorectal cancer and implications for prognosis. Biomarkers in medicine. 2015;9(4):349-61.
132. Ong CW, Chong PY, McArt DG, Chan JY, Tan HT, Kumar AP, et al. The prognostic value of the stem-like group in colorectal cancer using a panel of immunohistochemistry markers. Oncotarget. 2015;6(14):12763.
133. Talebi A, Kianersi K, Beiraghdar M. Comparison of gene expression of SOX2 and OCT4 in normal tissue, polyps, and colon adenocarcinoma using immunohistochemical staining. Advanced biomedical research. 2015;4.
134. Long W, Zhao W, Ning B, Huang J, Chu J, Li L, et al. PHF20 collaborates with PARP1 to promote stemness and aggressiveness of neuroblastoma cells through activation of SOX2 and OCT4. Journal of molecular cell biology. 2018;10(2):147-60.
135. Rad A, Farshchian M, Forghanifard MM, Matin MM, Bahrami AR, Geerts D, et al. Predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma. Tumor Biology. 2016;37(2):1715-25.
136. Madani GK, Rad A, Molavi M, Khales SA, Abbaszadegan MR, Forghanifard MM. Predicting the Correlation of EZH2 and Cancer Stem Cell Markers in Esophageal Squamous Cell Carcinoma. Journal of gastrointestinal cancer. 2018;49(4):437-41.
137. Liu X, Ma M, Duan X, Zhang H, Yang M. Knockdown of OCT4 may sensitize NSCLC cells to cisplatin. Clinical and Translational Oncology.2017;19(5):587-92.
2. Zhu R, Yang Y, Tian Y, Bai J, Zhang X, Li X, et al. Ascl2 knockdown results in tumor growth arrest by miRNA-302b-related inhibition of colon cancer progenitor cells. PloS one. 2012;7(2):e32170.
3. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. cell. 2007;131(5):861-72.
4. Rassouli FB, Matin MM, Bahrami AR, Ghaffarzadegan K, Cheshomi H, Lari S, et al. Evaluating stem and cancerous biomarkers in CD15+ CD44+ KYSE30 cells. Tumor Biology. 2013;34(5):2909-20.
5. Mueller M, Hermann PC, Liebau S, Weidgang C, Seufferlein T, Kleger A, et al. The role of pluripotency factors to drive stemness in gastrointestinal cancer. Stem cell research. 2016;16(2):349-57.
6. Lu X, Mazur SJ, Lin T, Appella E, Xu Y. The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis. Oncogene. 2014;33(20):2655.
7. Bornschein J, Tóth K, Selgrad M, Kuester D, Wex T, Molnár B, et al. Dysregulation of CDX1, CDX2 and SOX2 in patients with gastric cancer also affects the non-malignant mucosa. Journal of clinical pathology. 2013;66(9):819-22.
8. Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature. 2013;501(7467):355.
9. Lu Y, Futtner C, Rock JR, Xu X, Whitworth W, Hogan BL, et al. Evidence that SOX2 overexpression is oncogenic in the lung. PloS one. 2010;5(6):e11022.
10. Tsukamoto T, Mizoshita T, Mihara M, Tanaka H, Takenaka Y, Yamamura Y, et al. Sox2 expression in human stomach adenocarcinomas with gastric and gastric‐and‐intestinal‐mixed phenotypes. Histopathology. 2005;46(6):649-58.
11. Amsterdam A, Raanan C, Schreiber L, Freyhan O, Fabrikant Y, Melzer E, et al. Differential localization of LGR5 and Nanog in clusters of colon cancer stem cells. Acta histochemica. 2013;115(4):320-9.
12. Raghoebir L, Bakker ER, Mills JC, et al. SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype. Journal of molecular cell biology. 2012;4(6):377-85.
13. Chen S, Xu Y, Chen Y, Li X, Mou W, Wang L, et al. SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells. PloS one. 2012;7(5):e36326.
14. Ibrahim EE, Babaei‐Jadidi R, Saadeddin A, Spencer‐Dene B, Hossaini S, Abuzinadah M, et al. Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1‐and TCF‐dependent mechanisms. Stem cells. 2012;30(10):2076-87.
15. Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Müller F, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC cancer. 2011;11(1):42.
16. Yasuda H, Tanaka K, Okita Y, Araki T, Saigusa S, Toiyama Y, et al. CD133, OCT4, and NANOG in ulcerative colitis-associated colorectal cancer. Oncology letters. 2011;2(6):1065-71.
17. Shirzadeh E, Najafi M, Nazarzadeh M, Fazli G, Falanji F, Aldaghi LS, et al. Expression of Pluripotency markers, SOX2 and OCT4, in pterygium development. Critical Reviews™ in Eukaryotic Gene Expression. 2018;28(2).
18. Amini S, Fathi F, Mobalegi J, Sofimajidpour H, Ghadimi T. The expressions of stem cell markers: Oct4, Nanog, Sox2, nucleostemin, Bmi, Zfx, Tcl1, Tbx3, Dppa4, and Esrrb in bladder, colon, and prostate cancer, and certain cancer cell lines. Anatomy & cell biology. 2014;47(1):1-11.
19. Zhang G, Ma L, Xie Y-K, Miao X-B, Jin C. Esophageal cancer tumorspheres involve cancer stem-like populations with elevated aldehyde dehydrogenase enzymatic activity. Molecular medicine reports. 2012;6(3):519-24.
20. Santagata S, Ligon KL, Hornick JL. Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. The American journal of surgical pathology. 2007;31(6):836-45.
21. Cheng L. Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer. 2004;101(9):2006-10.
22. Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Annals of surgical oncology. 2009;16(12):3488-98.
23. Kim R-J, Nam J-S. OCT4 expression enhances features of cancer stem cells in a mouse model of breast cancer. Laboratory animal research. 2011;27(2):147-52.
24. Chen J, Pan Y, He B, Ying H, Wang F, Sun H, et al. Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells. International journal of oncology. 2015;47(4):1476-84.
25. Schöler HR. Octamania: the POU factors in murine development. Trends in genetics: TIG. 1991;7(10):323-9.
26. Brehm A, Ohbo K, Schöler H. The carboxy-terminal transactivation domain of Oct-4 acquires cell specificity through the POU domain. Molecular and cellular biology. 1997;17(1):154-62.
27. Pan GJ, Chang ZY, Schöler HR, Duanqing P. Stem cell pluripotency and transcription factor Oct4. Cell research. 2002;12(5-6):321.
28. Schöler H, Dressler GR, Balling R, Rohdewohld H, Gruss P. Oct‐4: a germline‐specific transcription factor mapping to the mouse t‐complex. The EMBO journal. 1990;9(7):2185-95.
29. Pesce M, Schöler HR. Oct‐4: gatekeeper in the beginnings of mammalian development. Stem cells. 2001;19(4):271-8.
30. Deb-Rinker P, Ly D, Jezierski A, Sikorska M, Walker PR. Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation. Journal of Biological Chemistry. 2005;280(8):6257-60.
31. Niwa H. Molecular mechanism to maintain stem cell renewal of ES cells. Cell structure and function. 2001;26(3):137-48.
32. Niwa H, Miyazaki J-i, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature genetics. 2000;24(4):372.
33. Tai M-H, Chang C-C, Olson LK, Trosko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26(2):495-502.
34. Gidekel S, Pizov G, Bergman Y, Pikarsky E. Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer cell. 2003;4(5):361-70.
35. Monk M, Holding C. Human embryonic genes re-expressed in cancer cells. Oncogene. 2001;20(56):8085.
36. LöNNROTH C, ANDeRSSON M, Asting AG, Nordgren S, Lundholm K. Preoperative low dose NSAID treatment influences the genes for stemness, growth, invasion and metastasis in colorectal cancer. International journal of oncology. 2014;45(6):2208-20.
37. Wang X, Dai J. Concise review: isoforms of OCT4 contribute to the confusing diversity in stem cell biology. Stem cells. 2010;28(5):885-93.
38. Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW. OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem cells. 2008;26(12):3068-74.
39. Costabile V, Duraturo F, Delrio P, Rega D, Pace U, Liccardo R, et al. Lithium chloride induces mesenchymal‑to‑epithelial reverting transition in primary colon cancer cell cultures. international journal of oncology. 2015;46(5):1913-23.
40. Chen Z, Xu WR, Qian H, Zhu W, Bu XF, Wang S, et al. Oct4, a novel marker for human gastric cancer. Journal of surgical oncology. 2009;99(7):414-9.
41. Cauffman G, Liebaers I, Van Steirteghem A, Van de Velde H. POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos. Stem cells. 2006;24(12):2685-91.
42. Lee J, Kim HK, Rho J-Y, Han Y-M, Kim J. The human OCT-4 isoforms differ in their ability to confer self-renewal. Journal of Biological Chemistry. 2006.
43. Grandér D, Johnsson P. Pseudogene-expressed RNAs: emerging roles in gene regulation and disease. Long Non-coding RNAs in Human Disease: Springer; 2015. p. 111-26.
44. An Y, Furber KL, Ji S. Pseudogenes regulate parental gene expression via ce RNA network. Journal of cellular and molecular medicine. 2017;21(1):185-92.
45. Pain D, Chirn G-W, Strassel C, Kemp DM. Multiple retropseudogenes from pluripotent cell-specific gene expression indicates a potential signature for novel gene identification. Journal of Biological Chemistry. 2005;280(8):6265-8.
46. Suo G, Han J, Wang X, Zhang J, Zhao Y, Zhao Y, et al. Oct4 pseudogenes are transcribed in cancers. Biochemical and biophysical research communications. 2005;337(4):1047-51.
47. Villodre ES, Kipper FC, Pereira MB, Lenz G. Roles of OCT4 in tumorigenesis, cancer therapy resistance and prognosis. Cancer treatment reviews. 2016;51:1-9.
48. Poursani EM, Soltani BM, Mowla SJ. Differential expression of OCT4 pseudogenes in pluripotent and tumor cell lines. Cell Journal (Yakhteh). 2016;18(1):28.
49. Poursani EM, Mehravar M, Soltani BM, Mowla SJ. Novel variant of OCT4B4 is differentially expressed in human embryonic stem and embryonic carcinoma cells. Gene. 2017;627:369-72.
50. Xu G, Yang L, Zhang W, Wei X. All the tested human somatic cells express both Oct4A and its pseudogenes but express Oct4A at much lower levels compared with its pseudogenes and human embryonic stem cells. Stem cells and development. 2015;24(13):1546-57.
51. Guo X, Tang Y. OCT4 pseudogenes present in human leukemia cells. Clinical and experimental medicine. 2012;12(4):207-16.
52. Wang L, Guo Z-Y, Zhang R, Xin B, Chen R, Zhao J, et al. Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma. Carcinogenesis. 2013;34(8):1773-81.
53. Napier KJ, Scheerer M, Misra S. Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities. World journal of gastrointestinal oncology. 2014;6(5):112.
54. Thrift AP. The epidemic of oesophageal carcinoma: where are we now? Cancer epidemiology. 2016;41:88-95.
55. Cantz T, Key G, Bleidiβel M, Gentile L, Han DW, Brenne A, et al. Absence of OCT4 expression in somatic tumor cell lines. Stem cells. 2008;26(3):692-7.
56. Zhou X, Huang G-R, Hu P. Over-expression of Oct4 in human esophageal squamous cell carcinoma. Molecules and cells. 2011;32(1):39-45.
57. He W, Wang Z, Wang Q, Fan Q, Shou C, Wang J, et al. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis. BMC cancer. 2009;9(1):426.
58. Nagaraja V, Eslick GD. Forthcoming prognostic markers for esophageal cancer: a systematic review and meta-analysis. Journal of gastrointestinal oncology. 2014;5(1):67.
59. Li C, Yan Y, Ji W, Bao L, Qian H, Chen L, et al. OCT4 positively regulates Survivin expression to promote cancer cell proliferation and leads to poor prognosis in esophageal squamous cell carcinoma. PloS one. 2012;7(11):e49693.
60. Li Z, Li X, Li C, Su Y, Fang W, Zhong C, et al. Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma. Cancer letters. 2014;354(1):77-86.
61. Li C, Zhu M, Lou X, Liu C, Chen H, Lin X, et al. Transcriptional factor OCT4 promotes esophageal cancer metastasis by inducing epithelial-mesenchymal transition through VEGF-C/VEGFR-3 signaling pathway. Oncotarget. 2017;8(42):71933.
62. Izadpanah MH, Abbaszadegan MR, Fahim Y, Forghanifard MM. Ectopic expression of TWIST1 upregulates the stemness marker OCT4 in the esophageal squamous cell carcinoma cell line KYSE30. Cellular & molecular biology letters. 2017;22(1):33.
63. Vaiphei K, Sinha SK, Kochhar R. Comparative analysis of Oct4 in different histological subtypes of esophageal squamous cell carcinomas in different clinical conditions. Asian Pac J Cancer Prev. 2014;15(8):3519-24.
64. Stock M, Otto F. Gene deregulation in gastric cancer. Gene. 2005;360(1):1-19.
65. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer management and research. 2018;10:239.
66. Rassouli FB, Matin MM, Bahrami AR, Ghaffarzadegan K, Sisakhtnezhad S, Cheshomi H, et al. SOX2 expression in gastrointestinal cancers of Iranian patients. The International journal of biological markers. 2015;30(3):315-20.
67. Yang L, Ping Y-F, Yu X, Qian F, Guo Z-J, Qian C, et al. Gastric cancer stem-like cells possess higher capability of invasion and metastasis in association with a mesenchymal transition phenotype. Cancer letters. 2011;310(1):46-52.
68. Fukuda K, Saikawa Y, Ohashi M, Kumagai K, Kitajima M, Okano H, et al. Tumor initiating potential of side population cells in human gastric cancer. International journal of oncology. 2009;34(5):1201-7.
69. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem cells. 2009;27(5):1006-20.
70. Liu J, Ma L, Xu J, Liu C, Zhang J, Liu J, et al. Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties. International journal of oncology. 2013;42(2):453-9.
71. Zhang X, Hua R, Wang X, Huang M, Gan L, Wu Z, et al. Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer. Oncotarget. 2016;7(9):9815.
72. Nosrati A, Naghshvar F, Khanari S. Cancer stem cell markers CD44, CD133 in primary gastric adenocarcinoma. International journal of molecular and cellular medicine. 2014;3(4):279.
73. Qiao XT, Gumucio DL. Current molecular markers for gastric progenitor cells and gastric cancer stem cells. Journal of gastroenterology. 2011;46(7):855-65.
74. Hong KJ, Wu DC, Cheng KH, Chen LT, Hung WC. RECK Inhibits Stemness Gene Expression and Tumorigenicity of Gastric Cancer Cells by Suppressing ADAM‐M ediated Notch1 Activation. Journal of cellular physiology. 2014;229(2):191-201.
75. Mao J, Liang Z, Zhang B, Yang H, Li X, Fu H, et al. UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell‐Exosome Promoted Gastric Cancer Progression via Wnt/β‐Catenin Pathway. Stem Cells. 2017;35(11):2267-79.
76. Mao J, Fan S, Ma W, Fan P, Wang B, Zhang J, et al. Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell death & disease. 2015;5(1):e1039.
77. Wang S, Liu F, Deng J, Cai X, Han J, Liu Q. Long noncoding RNA ROR regulates proliferation, invasion, and stemness of gastric cancer stem cell. Cellular Reprogramming (Formerly" Cloning and Stem Cells"). 2016;18(5):319-26.
78. Li N, Deng W, Ma J, Wei B, Guo K, Shen W, et al. Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Medical oncology. 2015;32(1):433.
79. Ji W, Jiang Z. Effect of shRNA‑mediated inhibition of Nanog gene expression on the behavior of human gastric cancer cells. Oncology letters. 2013;6(2):367-74.
80. Zhan Y-y, He J-p, Chen H-z, Wang W-j, Cai J-c. Orphan receptor TR3 is essential for the maintenance of stem-like properties in gastric cancer cells. Cancer letters. 2013;329(1):37-44.
81. Nishii T, Yashiro M, Shinto O, Sawada T, Ohira M, Hirakawa K. Cancer stem cell‐like SP cells have a high adhesion ability to the peritoneum in gastric carcinoma. Cancer science. 2009;100(8):1397-402.
82. Lin T, Ding Y-Q, Li J-M. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Medical oncology. 2012;29(2):878-85.
83. Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. International journal of cancer. 2011;128(11):2645-52.
84. Hayashi H, Arao T, Togashi Y, Kato H, Fujita Y, De Velasco M, et al. The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. Oncogene. 2015;34(2):199.
85. Chen B, Zhu Z, Li L, Ye W, Zeng J, Gao J, et al. Effect of overexpression of Oct4 and Sox2 genes on the biological and oncological characteristics of gastric cancer cells. OncoTargets and therapy. 2019;12:4667.
86. Kong D, Su G, Zha L, Zhang H, Xiang J, Xu W, et al. Coexpression of HMGA2 and Oct4 predicts an unfavorable prognosis in human gastric cancer. Medical oncology. 2014;31(8):130.
87. Guo J, Wang B, Fu Z, Wei J, Lu W. Hypoxic microenvironment induces EMT and upgrades stem-like properties of gastric cancer cells. Technology in cancer research & treatment. 2016;15(1):60-8.
88. Chen X-L, Chen X-Z, Wang Y-G, He D, Lu Z-H, Liu K, et al. Clinical significance of putative markers of cancer stem cells in gastric cancer: A retrospective cohort study. Oncotarget. 2016;7(38):62049.
89. Wang X-F, Zhang X-W, Hua R-X, Du Y-Q, Huang M-Z, Liu Y, et al. Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer. Oncotarget. 2016;7(39):63352.
90. Zhou G-X, Li X-Y, Zhang Q, Zhao K, Zhang C-P, Xue C-H, et al. Effects of the hippo signaling pathway in human gastric cancer. Asian Pacific journal of cancer prevention. 2013;14(9):5199-205.
91. Zhang Y, Zhang X, Wang X, Gan L, Yu G, Chen Y, et al. Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinal-type gastric cancer tumorigenicity through the downregulation of Oct4. Cancer letters. 2012;321(1):45-54.
92. Al-Marzoqee FY, Khoder G, Al-Awadhi H, John R, Beg A, Vincze A, et al. Upregulation and inhibition of the nuclear translocation of Oct4 during multistep gastric carcinogenesis. International journal of oncology. 2012;41(5):1733-43.
93. Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi REM, Corcione F. Worldwide burden of colorectal cancer: a review. Updates in surgery. 2016;68(1):7-11.
94. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106.
95. Dalerba P, Dylla SJ, Park I-K, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proceedings of the National Academy of Sciences. 2007;104(24):10158-63.
96. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111.
97. Zeuner A, Todaro M, Stassi G, De Maria R. Colorectal cancer stem cells: from the crypt to the clinic. Cell stem cell. 2014;15(6):692-705.
98. Liu Y-H, Li Y, Liu X-H, Sui H-M, Liu Y-X, Xiao Z-Q, et al. A signature for induced pluripotent stem cell–associated genes in colorectal cancer. Medical Oncology. 2013;30(1):426.
99. Dewi DL, Ishii H, Haraguchi N, Nishikawa S, Kano Y, Fukusumi T, et al. Dicer 1, ribonuclease type III modulates a reprogramming effect in colorectal cancer cells. International journal of molecular medicine. 2012;29(6):1060-4.
100. Chen S, Song X, Chen Z, Li X, Li M, Liu H, et al. CD133 expression and the prognosis of colorectal cancer: a systematic review and meta-analysis. PloS one. 2013;8(2):e56380.
101. Sedlar IT, Petricevic J, Saraga-Babic M, Pintaric I, Vukojevic K. Apoptotic pathways and stemness in the colorectal epithelium and lamina propria mucosae during the human embryogenesis and carcinogenesis. Acta histochemica. 2016;118(7):693-703.
102. Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell stem cell. 2014;14(3):342-56.
103. Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem cells. 2012;30(11):2378-86.
104. Jung P, Sato T, Merlos-Suárez A, Barriga FM, Iglesias M, Rossell D, et al. Isolation and in vitro expansion of human colonic stem cells. Nature medicine. 2011;17(10):1225.
105. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer research. 2009;69(8):3382-9.
106. Koshkin S, Danilova A, Raskin G, Petrov N, Bajenova O, O’Brien SJ, et al. Primary cultures of human colon cancer as a model to study cancer stem cells. Tumor Biology. 2016;37(9):12833-42.
107. Saiki Y, Ishimaru S, Mimori K, Takatsuno Y, Nagahara M, Ishii H, et al. Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Annals of surgical oncology. 2009;16(9):2638-44.
108. Shi Z, Bai R, Fu Z-x, Zhu Y-l, Wang R-f, Zheng S. Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells. Journal of Zhejiang University SCIENCE B. 2012;13(1):11-9.
109. Liu R-l, Zhang Z-h, Zhao W-m, Meng W, Qi S-y, Jing L, et al. Expression of nucleostemin in prostate cancer and its effect on the proliferation of PC-3 cells. Chinese medical journal. 2008;121(4):299-304.
110. Motzer RJ, Escudier B, Oudard S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma. Cancer. 2010;116(18):4256-65.
111. Munro MJ, Wickremesekera SK, Peng L, Marsh RW, Itinteang T, Tan ST. Cancer stem cell subpopulations in primary colon adenocarcinoma. PloS one. 2019;14(9):e0221963.
112. Koren A, Rijavec M, Kern I, Sodja E, Korosec P, Cufer T. BMI1, ALDH1A1, and CD133 transcripts connect epithelial-mesenchymal transition to cancer stem cells in lung carcinoma. Stem cells international. 2016;2016.
113. Litwin M, Dubis J, ARCZYŃSKA K, Piotrowska A, Frydlewicz A, Karczewski M, et al. Correlation of HIWI and HILI expression with cancer stem cell markers in colorectal cancer. Anticancer research. 2015;35(6):3317-24.
114. Ghodsi M, Jafarian AH, Montazer M, Sadeghian MH, Forghanifard MM. Diagnostic clinical relevance of developmental pluripotency-associated 2 (DPPA2) in colorectal cancer. International Journal of Surgery. 2015;13:193-7.
115. Padín-Iruegas M-E, Herranz-Carnero M, Aguin-Losada S, Brozos-Vazquez E, Anido-Herranz U, Antunez-Lopez J-R, et al. Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer. Oncology reports. 2013;29(6):2467-72.
116. Lemos C, Hardt MS, Juneja M, Voss C, Förster S, Jerchow B, et al. MACC1 induces tumor progression in transgenic mice and colorectal cancer patients via increased pluripotency markers Nanog and Oct4. Clinical Cancer Research. 2016.
117. Fidalgo M, Faiola F, Pereira C-F, Ding J, Saunders A, Gingold J, et al. Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. Proceedings of the National Academy of Sciences. 2012;109(40):16202-7.
118. Wang ZX, Teh CHL, Chan CMY, et al. The transcription factor Zfp281 controls embryonic stem cell pluripotency by direct activation and repression of target genes. Stem Cells. 2008;26(11):2791-9.
119. Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, et al. A protein interaction network for pluripotency of embryonic stem cells. nature. 2006;444(7117):364.
120. Takeuchi A, Mishina Y, Miyaishi O, Kojima E, Hasegawa T, Isobe K-i. Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells during mouse embryogenesis. Nature genetics. 2003;33(2):172.
121. Chang C-J, Chien Y, Lu K-H, Chang S-C, Chou Y-C, Huang C-S, et al. Oct4-related cytokine effects regulate tumorigenic properties of colorectal cancer cells. Biochemical and biophysical research communications. 2011;415(2):245-51.
122. Gazouli M, Roubelakis MG, Theodoropoulos GE, Papailiou J, Vaiopoulou A, Pappa KI, et al. OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer. Molecular carcinogenesis. 2012;51(2):165-73.
123. Dai X, Ge J, Wang X, Qian X, Zhang C, Li X. OCT4 regulates epithelial-mesenchymal transition and its knockdown inhibits colorectal cancer cell migration and invasion. Oncology reports. 2013;29(1):155-60.
124. Wang R, Bhattacharya R, Ye X, Fan F, Boulbes DR, Xia L, et al. Endothelial cells activate the cancer stem cell‐associated NANOGP8 pathway in colorectal cancer cells in a paracrine fashion. Molecular oncology. 2017;11(8):1023-34.
125. Williamson JM, Thairu N, Katsoulas N, Stamp G, Ahmad R, du Potet E, et al. Impact of portal vein embolization on expression of cancer stem cell markers in regenerated liver and colorectal liver metastases. Scandinavian journal of gastroenterology. 2010;45(12):1472-9.
126. Miranda PV, Allaire A, Sosnik J, Visconti PE. Localization of low-density detergent-resistant membrane proteins in intact and acrosome-reacted mouse sperm. Biology of reproduction. 2009;80(5):897-904.
127. Batsaikhan B-E, Yoshikawa K, Kurita N, Iwata T, Takasu C, Kashihara H, et al. Cyclopamine decreased the expression of sonic hedgehog and its downstream genes in colon cancer stem cells. Anticancer research. 2014;34(11):6339-44.
128. Liang K, Zhou G, Zhang Q, Li J, Zhang C. Expression of hippo pathway in colorectal cancer. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association. 2014;20(3):188.
129. Wen K, Fu Z, Wu X, Feng J, Chen W, Qian J. Oct-4 is required for an antiapoptotic behavior of chemoresistant colorectal cancer cells enriched for cancer stem cells: effects associated with STAT3/Survivin. Cancer letters. 2013;333(1):56-65.
130. Khorrami S, Hosseini AZ, Mowla SJ, Malekzadeh R. Verification of ALDH activity as a biomarker in colon cancer stem cells-derived HT-29 cell line. Iranian journal of cancer prevention. 2015;8(5).
131. Voutsadakis IA. Pluripotency transcription factors in the pathogenesis of colorectal cancer and implications for prognosis. Biomarkers in medicine. 2015;9(4):349-61.
132. Ong CW, Chong PY, McArt DG, Chan JY, Tan HT, Kumar AP, et al. The prognostic value of the stem-like group in colorectal cancer using a panel of immunohistochemistry markers. Oncotarget. 2015;6(14):12763.
133. Talebi A, Kianersi K, Beiraghdar M. Comparison of gene expression of SOX2 and OCT4 in normal tissue, polyps, and colon adenocarcinoma using immunohistochemical staining. Advanced biomedical research. 2015;4.
134. Long W, Zhao W, Ning B, Huang J, Chu J, Li L, et al. PHF20 collaborates with PARP1 to promote stemness and aggressiveness of neuroblastoma cells through activation of SOX2 and OCT4. Journal of molecular cell biology. 2018;10(2):147-60.
135. Rad A, Farshchian M, Forghanifard MM, Matin MM, Bahrami AR, Geerts D, et al. Predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma. Tumor Biology. 2016;37(2):1715-25.
136. Madani GK, Rad A, Molavi M, Khales SA, Abbaszadegan MR, Forghanifard MM. Predicting the Correlation of EZH2 and Cancer Stem Cell Markers in Esophageal Squamous Cell Carcinoma. Journal of gastrointestinal cancer. 2018;49(4):437-41.
137. Liu X, Ma M, Duan X, Zhang H, Yang M. Knockdown of OCT4 may sensitize NSCLC cells to cisplatin. Clinical and Translational Oncology.2017;19(5):587-92.
| Files | ||
| Issue | Vol 19, No 3 (2020) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v19i3.3451 | |
| PMID | 32615657 | |
| Keywords | ||
| Colorectal cancer Esophageal neoplasms Stomach neoplasms | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Cheshomi H, Gholami O, Peyroshabani B, Rad A. Impact of OCT4 and Its Related Signaling Pathways on Gastrointestinal Cancers: Focusing on Targeted Therapy. Iran J Allergy Asthma Immunol. 2020;19(3):229-242.
