Abstract
Oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck, ranks sixth worldwide in terms of cancers with the most negative impact, owing to tumor relapse rates, cervical lymphnode metastasis, and the lack of an efficacious systemic therapy. Its prognosis is poor, and its mortality rate is high. Octamer-binding transcription factor 4 (OCT4) is a member of the Pit-Oct-Unc (POU) family and is a key reprogramming factor that produces a marked effect in preserving the pluripotency and self-renewal state of embryonic stem cells (ESCs). According to recent studies, OCT4 participates in retaining the survival of OSCC cancer stem cells (CSCs), which has far-reaching implications for the occurrence, recurrence, metastasis, and prognosis of oral carcinogenesis. Therefore, we summarize the structure, subtypes, and function of OCT4 as well as its role in the occurrence, progression, and prognosis of OSCC.
摘要
口腔鳞状细胞癌(OSCC)是一种常见的头颈部恶性肿瘤。由于肿瘤复发率高、颈部淋巴结转移和缺乏有效的全身治疗手段,OSCC在全球最具负面影响的癌症中排名第六。其预后差,死亡率高。八聚体结合转录因子4(OCT4)是Pit-Oct-Unc(POU)家族的成员,是一种关键的重编程因子,在保持胚胎干细胞(ESCs)的多能性和自我更新状态方面具有显著作用。最近的研究表明,OCT4参与维持OSCC癌症干细胞(CSC)的存活,对口腔癌的发生、复发、转移和预后具有深远的影响。因此,我们总结了OCT4的结构、亚型、功能及其在OSCC的发生、发展和预后中的作用。
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References
Al-Magsoosi MJN, Lambert DW, Ali Khurram S, et al., 2021. Oral cancer stem cells drive tumourigenesis through activation of stromal fibroblasts. Oral Dis, 27(6):1383–1393. https://doi.org/10.1111/odi.13513
Bai XP, Ni J, Beretov J, et al., 2018. Cancer stem cell in breast cancer therapeutic resistance. Cancer Treat Rev, 69:152–163. https://doi.org/10.1016/j.ctrv.2018.07.004
Baillie R, Tan ST, Itinteang T, 2017. Cancer stem cells in oral cavity squamous cell carcinoma: a review. Front Oncol, 7:112. https://doi.org/10.3389/fonc.2017.00112
Basati G, Mohammadpour H, Emami Razavi A, 2020. Association of high expression levels of SOX2, NANOG, and OCT4 in gastric cancer tumor tissues with progression and poor prognosis. J Gastrointest Cancer, 51(1):41–47. https://doi.org/10.1007/s12029-018-00200-x
Benson RA, Lowrey JA, Lamb JR, et al., 2004. The Notch and Sonic hedgehog signalling pathways in immunity. Mol Immunol, 41(6–7):715–725. https://doi.org/10.1016/j.molimm.2004.04.017
Bhardwaj G, Murdoch B, Wu D, et al., 2001. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol, 2(2):172–180. https://doi.org/10.1038/84282
Bourguignon LYW, Wong G, Earle C, et al., 2012. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem, 287(39):32800–32824. https://doi.org/10.1074/jbc.M111.308528
Bray F, Ferlay J, Soerjomataram I, et al., 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6):394–424. https://doi.org/10.3322/caac.21492
Cai JH, He BX, Li XM, et al., 2016. Regulation of tumorigenesis in oral epithelial cells by defined reprogramming factors Oct4 and Sox2. Oncol Rep, 36(2):651–658. https://doi.org/10.3892/or.2016.4851
Cao YW, Tian WT, Cao L, et al., 2022. Generation of an induced pluripotent stem cell JTUi005-A from a patient with neuronal intranuclear inclusion disease. Stem Cell Res, 65:102938. https://doi.org/10.1016/j.scr.2022.102938
Cauffman G, Liebaers I, van Steirteghem A, et al., 2006. POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos. Stem Cells, 24(12):2685–2691. https://doi.org/10.1634/stemcells.2005-0611
Chang CC, Shieh GS, Wu P, et al., 2008. Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells. Cancer Res, 68(15):6281–6291. https://doi.org/10.1158/0008-5472.CAN-08-0094
Chen BR, Zhu ZP, Li LL, et al., 2019. Effect of overexpression of Oct4 and Sox2 genes on the biological and oncological characteristics of gastric cancer cells. Onco Targets Ther, 12:4667–4682. https://doi.org/10.2147/OTT.S209734
Chen TM, Huang CM, Hsieh MS, et al., 2022. TRPM7 via calcineurin/NFAT pathway mediates metastasis and chemotherapeutic resistance in head and neck squamous cell carcinoma. Aging, 14(12):5250–5270. https://doi.org/10.18632/aging.204154
Chien CS, Wang ML, Chu PY, et al., 2015. Lin28B/Let-7 regulates expression of Oct4 and Sox2 and reprograms oral squamous cell carcinoma cells to a stem-like state. Cancer Res, 75(12):2553–2565. https://doi.org/10.1158/0008-5472.CAN-14-2215
Chiou SH, Yu CC, Huang CY, et al., 2008. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res, 14(13):4085–4095. https://doi.org/10.1158/1078-0432.CCR-07-4404
Curtarelli RB, Gonçalves JM, dos Santos LGP, et al., 2018. Expression of cancer stem cell biomarkers in human head and neck carcinomas: a systematic review. Stem Cell Rev Rep, 14(6):769–784. https://doi.org/10.1007/s12015-018-9839-4
da Silva SD, Hier M, Mlynarek A, et al., 2012. Recurrent oral cancer: current and emerging therapeutic approaches. Front Pharmacol, 3:149. https://doi.org/10.3389/fphar.2012.00149
Dai XM, Guo YX, Hu Y, et al., 2021. Immunotherapy for targeting cancer stem cells in hepatocellular carcinoma. Theranostics, 11(7):3489–3501. https://doi.org/10.7150/thno.54648
Deng KY, Liu L, Tan XM, et al., 2020. Wip1 promotes cancer stem cell properties by inhibiting p38 MAPK in NSCLC. Signal Transduct Target Ther, 5:36. https://doi.org/10.1038/s41392-020-0126-x
Diévart A, Beaulieu N, Jolicoeur P, 1999. Involvement of Notch1 in the development of mouse mammary tumors. Oncogene, 18(44):5973–5981. https://doi.org/10.1038/sj.onc.1202991
Fan ZN, Li MX, Chen XB, et al., 2017. Prognostic value of cancer stem cell markers in head and neck squamous cell carcinoma: a meta-analysis. Sci Rep, 7:43008. https://doi.org/10.1038/srep43008
Feng J, Li YX, Wen N, 2021. Characterization of cancer stem cell characteristics and development of a prognostic stemness index cell-related signature in oral squamous cell carcinoma. Dis Markers, 2021:1571421. https://doi.org/10.1155/2021/1571421
Fu TY, Hsieh IC, Cheng JT, et al., 2016. Association of OCT4, SOX2, and NANOG expression with oral squamous cell carcinoma progression. J Oral Pathol Med, 45(2):89–95. https://doi.org/10.1111/jop.12335
Fujii M, Katase N, Lefeuvre M, et al., 2011. Dickkopf (Dkk)-3 and β-catenin expressions increased in the transition from normal oral mucosal to oral squamous cell carcinoma. J Mol Histol, 42(6):499–504. https://doi.org/10.1007/s10735-011-9357-z
Gat U, Dasgupta R, Degenstein L, et al., 1998. De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated β-catenin in skin. Cell, 95(5):605–614. https://doi.org/10.1016/s0092-8674(00)81631-1
Ghazi N, Aali N, Shahrokhi VR, et al., 2020. Relative expression of SOX2 and OCT4 in oral squamous cell carcinoma and oral epithelial dysplasia. Rep Biochem Mol Biol, 9(2):171–179. https://doi.org/10.29252/rbmb.9.2.171
Gimple RC, Bhargava S, Dixit D, et al., 2019. Glioblastoma stem cells: lessons from the tumor hierarchy in a lethal cancer. Genes Dev, 33(11–12):591–609. https://doi.org/10.1101/gad.324301.119
Gliagias V, Wotman M, Herman SW, et al., 2019. Investigating the role of octamer binding transcription factor-4 (Oct-4) in oral cavity squamous cell carcinoma: a systematic review and meta-analysis. Am J Otolaryngol, 40(2):282–288. https://doi.org/10.1016/j.amjoto.2018.12.011
Griffin JD, Lowenberg B, 1986. Clonogenic cells in acute myeloblastic leukemia. Blood, 68(6):1185–1195. https://doi.org/10.1182/blood.V68.6.1185.1185
Gupta S, Kumar P, Das BC, 2021. HPV+ve/−ve oral-tongue cancer stem cells: a potential target for relapse-free therapy. Transl Oncol, 14(1):100919. https://doi.org/10.1016/j.tranon.2020.100919
Han D, Wu GM, Chen R, et al., 2022. A balanced Oct4 interactome is crucial for maintaining pluripotency. Sci Adv, 8(7):eabe4375. https://doi.org/10.1126/sciadv.abe4375
He SQ, Zhang W, Li X, et al., 2021. Oral squamous cell carcinoma (OSCC)-derived exosomal MiR-221 targets and regulates phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to promote human umbilical vein endothelial cells migration and tube formation. Bioengineered, 12(1):2164–2174. https://doi.org/10.1080/21655979.2021.1932222
Heng WS, Gosens R, Kruyt FAE, 2019. Lung cancer stem cells: origin, features, maintenance mechanisms and therapeutic targeting. Biochem Pharmacol, 160:121–133. https://doi.org/10.1016/j.bcp.2018.12.010
Herr W, Cleary MA, 1995. The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev, 9(14):1679–1693. https://doi.org/10.1101/gad.9.14.1679
Huang CF, Xu XR, Wu TF, et al., 2014. Correlation of ALDH1, CD44, OCT4 and SOX2 in tongue squamous cell carcinoma and their association with disease progression and prognosis. J Oral Pathol Med, 43(7):492–498. https://doi.org/10.1111/jop.12159
Huang GZ, Wu QQ, Zheng ZN, et al., 2020. M6A-related bio-informatics analysis reveals that HNRNPC facilitates progression of OSCC via EMT. Aging, 12(12):11667–11684. https://doi.org/10.18632/aging.103333
Ilia K, Shakiba N, Bingham T, et al., 2023. Synthetic genetic circuits to uncover and enforce the OCT4 trajectories of successful reprogramming of human fibroblasts. bioRxiv, preprint. https://doi.org/10.1101/2023.01.25.525529
Iwai S, Yonekawa A, Harada C, et al., 2010. Involvement of the Wnt-β-catenin pathway in invasion and migration of oral squamous carcinoma cells. Int J Oncol, 37(5):1095–1103. https://doi.org/10.3892/ijo_00000761
Karanu FN, Murdoch B, Gallacher L, et al., 2000. The Notch ligand Jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med, 192(9):1365–1372. https://doi.org/10.1084/jem.192.9.1365
Karhadkar SS, Bova GS, Abdallah N, et al., 2004. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature, 431(7009):707–712. https://doi.org/10.1038/nature02962
Khan W, Augustine D, Rao RS, et al., 2018. Stem cell markers SOX-2 and OCT-4 enable to resolve the diagnostic dilemma between ameloblastic carcinoma and aggressive solid multicystic ameloblastoma. Adv Biomed Res, 7:149. https://doi.org/10.4103/abr.abr_135_18
Kim RJ, Nam JS, 2011. OCT4 expression enhances features of cancer stem cells in a mouse model of breast cancer. Lab Anim Res, 27(2):147–152. https://doi.org/10.5625/lar.2011.27.2.147
Kong QY, Liu L, Huang YJ, et al., 2014. The effect of octamer-binding transcription factor 4B1 on microRNA signals in human dental pulp cells with inflammatory response. J Endod, 40(1):101–108. https://doi.org/10.1016/j.joen.2013.09.030
Kotoula V, Papamichos SI, Lambropoulos AF, 2008. Revisiting OCT4 expression in peripheral blood mononuclear cells. Stem Cells, 26(1):290–291. https://doi.org/10.1634/stemcells.2007-0726
Lathia JD, Mack SC, Mulkearns-Hubert EE, et al., 2015. Cancer stem cells in glioblastoma. Genes Dev, 29(12):1203–1217. https://doi.org/10.1101/gad.261982.115
Lee J, Kim HK, Rho JY, et al., 2006. The human OCT-4 isoforms differ in their ability to confer self-renewal. J Biol Chem, 281(44):33554–33565. https://doi.org/10.1074/jbc.M603937200
Lee SH, Kieu C, Martin CE, et al., 2019. NFATc3 plays an oncogenic role in oral/oropharyngeal squamous cell carcinomas by promoting cancer stemness via expression of OCT4. Oncotarget, 10(23):2306–2319. https://doi.org/10.18632/oncotarget.26774
Li H, Wang LW, Shi SP, et al., 2019. The prognostic and clinicopathologic characteristics of OCT4 and lung cancer: a meta-analysis. Curr Mol Med, 19(1):54–75. https://doi.org/10.2174/1566524019666190308163315
Liu L, Huang R, Yang RQ, et al., 2017. OCT4B1 regulates the cellular stress response of human dental pulp cells with inflammation. Biomed Res Int, 2017:2756891. https://doi.org/10.1155/2017/2756891
Liu LK, Jiang XY, Zhou XX, et al., 2010. Upregulation of vimentin and aberrant expression of E-cadherin/β-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome. Mod Pathol, 23(2):213–224. https://doi.org/10.1038/modpathol.2009.160
Liu YC, Yeh CT, Lin KH, 2020. Cancer stem cell functions in hepatocellular carcinoma and comprehensive therapeutic strategies. Cells, 9(6):1331. https://doi.org/10.3390/cells9061331
Liu YF, Yang M, Luo JJ, et al., 2020. Radiotherapy targeting cancer stem cells “awakens” them to induce tumour relapse and metastasis in oral cancer. Int J Oral Sci, 12:19. https://doi.org/10.1038/s41368-020-00087-0
Lu CS, Shieh GS, Wang CT, et al., 2017. Chemotherapeutics-induced Oct4 expression contributes to drug resistance and tumor recurrence in bladder cancer. Oncotarget, 8(19):30844–30858. https://doi.org/10.18632/oncotarget.9602
Lu CS, Shiau AL, Su BH, et al., 2020. Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer. J Hematol Oncol, 13:62. https://doi.org/10.1186/s13045-020-00887-1
Lu HQ, Xie YYR, Tran L, et al., 2020. Chemotherapy-induced S100A10 recruits KDM6A to facilitate OCT4-mediated breast cancer stemness. J Clin Invest, 130(9):4607–4623. https://doi.org/10.1172/JCI138577
Ma Z, Zhang C, Liu XT, et al., 2020. Characterisation of a subpopulation of CD133+ cancer stem cells from Chinese patients with oral squamous cell carcinoma. Sci Rep, 10:8875. https://doi.org/10.1038/s41598-020-64947-9
Mishra S, Tiwari V, Arora A, et al., 2020. Increased expression of Oct4, Nanog and CD24 predicts poor response to chemo-radiotherapy and unfavourable prognosis in locally advanced oral squamous cell carcinoma. Asian Pac J Cancer Prev, 21(9):2539–2547. https://doi.org/10.31557/APJCP.2020.2.1.9.2539
Moro JDS, Maroneze MC, Ardenghi TM, et al., 2018. Oral and oropharyngeal cancer: epidemiology and survival analysis. Einstein (Sao Paulo), 16(2):eAO4248. https://doi.org/10.1590/S1679-45082018AO4248
Naini FB, Aminishakib P, Abdollahi A, et al., 2019. Relative expression of OCT4, SOX2 and NANOG in oral squamous cell carcinoma versus adjacent non-tumor tissue. Asian Pac J Cancer Prev, 20(6):1649–1654. https://doi.org/10.31557/APJCP.2019.20.6.1649
Nam Y, Aster JC, Blacklow SC, 2002. Notch signaling as a therapeutic target. Curr Opin Chem Biol, 6(4):501–509. https://doi.org/10.1016/s1367-5931(02)00346-0
Nathansen J, Lukiyanchuk V, Hein L, et al., 2021. Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L. Oncogene, 40(24):4214–4228. https://doi.org/10.1038/s41388-021-01842-1
Nguyen A, Kim AH, Kang MK, et al., 2022. Chronic alcohol exposure promotes cancer stemness and glycolysis in oral/oropharyngeal squamous cell carcinoma cell lines by activating NFAT signaling. Int J Mol Sci, 23(17):9779. https://doi.org/10.3390/ijms23179779
Nichols J, Zevnik B, Anastassiadis K, et al., 1998. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 95(3):379–391. https://doi.org/10.1016/s0092-8674(00)81769-9
Nickoloff BJ, Osborne BA, Miele L, 2003. Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents. Oncogene, 22(42):6598–6608. https://doi.org/10.1038/sj.onc.1206758
Nör C, Zhang ZC, Warner KA, et al., 2014. Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer. Neoplasia, 16(2):137–146 W8. https://doi.org/10.1593/neo.131744
Noto Z, Yoshida T, Okabe M, et al., 2013. CD44 and SSEA-4 positive cells in an oral cancer cell line HSC-4 possess cancer stem-like cell characteristics. Oral Oncol, 49(8):787–795. https://doi.org/10.1016/j.oraloncology.2013.04.012
Okamoto A, Chikamatsu K, Sakakura K, et al., 2009. Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck. Oral Oncol, 45(7):633–639. https://doi.org/10.1016/j.oraloncology.2008.10.003
Olivares-Urbano MA, Griñán-Lisón C, Marchal JA, et al., 2020. CSC radioresistance: a therapeutic challenge to improve radiotherapy effectiveness in cancer. Cells, 9(7):1651. https://doi.org/10.3390/cells9071651
Olsen CL, Hsu PP, Glienke J, et al., 2004. Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors. BMC Cancer, 4:43. https://doi.org/10.1186/1471-2407-4-43
Oshimori N, 2020. Cancer stem cells and their niche in the progression of squamous cell carcinoma. Cancer Sci, 111(11):3985–3992. https://doi.org/10.1111/cas.14639
Pai S, Yadav VK, Kuo KT, et al., 2021. PDK1 inhibitor BX795 improves cisplatin and radio-efficacy in oral squamous cell carcinoma by downregulating the PDK1/CD47/Akt-mediated glycolysis signaling pathway. Int J Mol Sci, 22(21):11492. https://doi.org/10.3390/ijms222111492
Pandian J, Panneerpandian P, Sekar BT, et al., 2022. OCT4-mediated transcription confers oncogenic advantage for a subset of gastric tumors with poor clinical outcome. Funct Integr Genomics, 22(6):1345–1360. https://doi.org/10.1007/s10142-022-00894-0
Pang X, Wang SS, Zhang M, et al., 2021. OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway. Cancer Immunol Immunother, 70(4):1015–1029. https://doi.org/10.1007/s00262-020-02741-2
Pesce M, Scholer HR, 2001. Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells, 19(4):271–278. https://doi.org/10.1634/stemcells.19-4-271
Quaglino E, Conti L, Cavallo F, 2020. Breast cancer stem cell antigens as targets for immunotherapy. Semin Immunol, 47:101386. https://doi.org/10.1016/j.smim.2020.101386
Rao RS, Raju KL, Augustine D, et al., 2020. Prognostic significance of ALDH1, Bmi1, and OCT4 expression in oral epithelial dysplasia and oral squamous cell carcinoma. Cancer Control, 27(1):1073274820904959. https://doi.org/10.1177/1073274820904959
Rasti A, Mehrazma M, Madjd Z, et al., 2018. Co-expression of cancer stem cell markers OCT4 and NANOG predicts poor prognosis in renal cell carcinomas. Sci Rep, 8:11739. https://doi.org/10.1038/s41598-018-30168-4
Ravindran G, Devaraj H, 2012. Aberrant expression of β-catenin and its association with ΔNp63, Notch-1, and clinicopathological factors in oral squamous cell carcinoma. Clin Oral Investig, 16(4):1275–1288. https://doi.org/10.1007/s00784-011-0605-0
Ravindran G, Sawant SS, Hague A, et al., 2015. Association of differential β-catenin expression with Oct-4 and nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis. Head Neck, 37(7):982–993. https://doi.org/10.1002/hed.23699
Reers S, Pfannerstill AC, Maushagen R, et al., 2014. Stem cell profiling in head and neck cancer reveals an Oct-4 expressing subpopulation with properties of chemoresistance. Oral Oncol, 50(3):155–162. https://doi.org/10.1016/j.oraloncology.2013.12.006
Reya T, Morrison SJ, Clarke MF, et al., 2001. Stem cells, cancer, and cancer stem cells. Nature, 414(6859):105–111. https://doi.org/10.1038/35102167
Rizzino A, Wuebben EL, 2016. Sox2/Oct4: a delicately balanced partnership in pluripotent stem cells and embryogenesis. Biochim Biophys Acta, 1859(6):780–791. https://doi.org/10.1016/j.bbagrm.2016.03.006
Rodini CO, Lopes NM, Lara VS, et al., 2017. Oral cancer stem cells - properties and consequences. J Appl Oral Sci, 25(6):708–715. https://doi.org/10.1590/1678-7757-2016-0665
Rodrigues MFSD, de Aquino Xavier FC, Andrade NP, et al., 2018. Prognostic implications of CD44, NANOG, OCT4, and BMI1 expression in tongue squamous cell carcinoma. Head Neck, 40(8):1759–1773. https://doi.org/10.1002/hed.25158
Roy S, Kar M, Roy S, et al., 2019. KLF4 expression in the surgical cut margin is associated with disease relapse of oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol, 128(2):154–165. https://doi.org/10.1016/j.oooo.2019.02.021
Satpute PS, Hazarey V, Ahmed R, et al., 2013. Cancer stem cells in head and neck squamous cell carcinoma: a review. Asian Pac J Cancer Prev, 14(10):5579–5587. https://doi.org/10.7314/apjcp.2013.14.10.5579
Sawant S, Gokulan R, Dongre H, et al., 2016. Prognostic role of Oct4, CD44 and c-Myc in radio-chemo-resistant oral cancer patients and their tumourigenic potential in immunodeficient mice. Clin Oral Invest, 20(1):43–56. https://doi.org/10.1007/s00784-015-1476-6
Sharifzad F, Ghavami S, Verdi J, et al., 2019. Glioblastoma cancer stem cell biology: potential theranostic targets. Drug Resist Updat, 42:35–45. https://doi.org/10.1016/j.drup.2018.03.003
Shen HF, Li YL, Huang SH, et al., 2022. A real-time pluripotency reporter for the long-term and real-time monitoring of pluripotency changes in induced pluripotent stem cells. Aging, 14(10):4445–4458. https://doi.org/10.18632/aging.204083
Shin KH, Kim RH, 2018. An updated review of oral cancer stem cells and their stemness regulation. Crit Rev Oncog, 23(3–4):189–200. https://doi.org/10.1615/CritRevOncog.2018027501
Siegel RL, Miller KD, Jemal A, 2019. Cancer statistics, 2019. CA Cancer J Clin, 69(1):7–34. https://doi.org/10.3322/caac.21551
Singh A, Srivastava AN, Akhtar S, et al., 2018. Correlation of CD133 and Oct-4 expression with clinicopathological and demographic parameters in oral squamous cell carcinoma patients. Natl J Maxillofac Surg, 9(1):8–13. https://doi.org/10.4103/njms.NJMS_60_17
Song J, Chang I, Chen Z, et al., 2010. Characterization of side populations in HNSCC: highly invasive, chemoresistant and abnormal Wnt signaling. PLoS ONE, 5(7):e11456. https://doi.org/10.1371/journal.pone.0011456
Sun L, Xu YR, Zhang XM, et al., 2020. Mesenchymal stem cells functionalized sonodynamic treatment for improving therapeutic efficacy and compliance of orthotopic oral cancer. Adv Mater, 32(48):e2005295. https://doi.org/10.1002/adma.202005295
Swain N, Thakur M, Pathak J, et al., 2020. SOX2, OCT4 and NANOG: the core embryonic stem cell pluripotency regulators in oral carcinogenesis. J Oral Maxillofac Pathol, 24(2):368–373. https://doi.org/10.4103/jomfp.JOMFP_22_20
Tahmasebi E, Alikhani M, Yazdanian A, et al., 2020. The current markers of cancer stem cell in oral cancers. Life Sci, 249:117483. https://doi.org/10.1016/j.lfs.2020.117483
Tegginamani AS, Shivakumar VH, Kallarakkal TG, et al., 2020. Analysis of octamer-binding transcription factor-4 expression in oral leukoplakia. J Oral Maxillofac Pathol, 24(2):400. https://doi.org/10.4103/jomfp.JOMFP_272_19
Thomaidou AC, Batsaki P, Adamaki M, et al., 2022. Promising biomarkers in head and neck cancer: the most clinically important miRNAs. Int J Mol Sci, 23(15):8257. https://doi.org/10.3390/ijms23158257
Tsai LL, Hu FW, Lee SS, et al., 2014. Oct4 mediates tumor initiating properties in oral squamous cell carcinomas through the regulation of epithelial-mesenchymal transition. PLoS ONE, 9(1):e87207. https://doi.org/10.1371/journal.pone.0087207
Tulake W, Yuemaier R, Sheng L, et al., 2018. Upregulation of stem cell markers ALDH1A1 and OCT4 as potential biomarkers for the early detection of cervical carcinoma. Oncol Lett, 16(5):5525–5534. https://doi.org/10.3892/ol.2018.9381
Unden AB, Holmberg E, Lundh-Rozell B, et al., 1996. Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the gorlin syndrome: different in vivo mechanisms of PTCH inactivation. Cancer Res, 56(20):4562–4565.
Varnum-Finney B, Xu LW, Brashem-Stein C, et al., 2000. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med, 6(11):1278–1281. https://doi.org/10.1038/81390
Vijayakumar G, Narwal A, Kamboj M, et al., 2020. Association of SOX2, OCT4 and WNT5A expression in oral epithelial dysplasia and oral squamous cell carcinoma: an immunohistochemical study. Head Neck Pathol, 14(3):749–757. https://doi.org/10.1007/s12105-019-01114-1
Wang YF, Cao Z, Liu FJ, et al., 2021. Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer. Open Life Sci, 16(1):1045–1052. https://doi.org/10.1515/biol-2021-0104
Wang YJ, Meng L, Hu HY, et al., 2011. Oct-4B isoform is differentially expressed in breast cancer cells: hypermethylation of regulatory elements of Oct-4A suggests an alternative promoter and transcriptional start site for Oct-4B transcription. Biosci Rep, 31(2):109–115. https://doi.org/10.1042/Bsr20100033
Wen KM, Fu ZX, Wu XY, et al., 2013. Oct-4 is required for an antiapoptotic behavior of chemoresistant colorectal cancer cells enriched for cancer stem cells: effects associated with STAT3/survivin. Cancer Lett, 333(1):56–65. https://doi.org/10.1016/j.canlet.2013.01.009
Wong MMT, Chan HY, Aziz NA, et al., 2021. Interplay of autophagy and cancer stem cells in hepatocellular carcinoma. Mol Biol Rep, 48(4):3695–3717. https://doi.org/10.1007/s11033-021-06334-9
Wu Q, Wu Z, Bao CY, et al., 2019. Cancer stem cells in esophageal squamous cell cancer (review). Oncol Lett, 18(5):5022–5032. https://doi.org/10.3892/ol.2019.10900
Xie WW, Yu J, Yin YJ, et al., 2022. OCT4 induces EMT and promotes ovarian cancer progression by regulating the PI3K/AKT/mTOR pathway. Front Oncol, 12:876257. https://doi.org/10.3389/fonc.2022.876257
Yang F, Xu J, Tang L, et al., 2017. Breast cancer stem cell: the roles and therapeutic implications. Cell Mol Life Sci, 74(6):951–966. https://doi.org/10.1007/s00018-016-2334-7
Yang PP, Li CS, Zhou Q, et al., 2022. Notum leads to potential pro-survival of OSCC through crosstalk between Shh and Wnt/β-catenin signaling via p-GSK3β. Int J Biochem Cell Biol, 153:106316. https://doi.org/10.1016/j.biocel.2022.106316
Yuan FJ, Zhou WB, Zou C, et al., 2010. Expression of Oct4 in HCC and modulation to wnt/β-catenin and TGF-β signal pathways. Mol Cell Biochem, 343(1–2):155–162. https://doi.org/10.1007/s11010-010-0509-3
Zhan T, Rindtorff N, Boutros M, 2017. Wnt signaling in cancer. Oncogene, 36(11):1461–1473. https://doi.org/10.1038/onc.2016.304
Zhang JM, Wei K, Jiang M, 2018. OCT4 but not SOX2 expression correlates with worse prognosis in surgical patients with triple-negative breast cancer. Breast Cancer, 25(4):447–455. https://doi.org/10.1007/s12282-018-0844-x
Zhang L, Meng X, Zhu XW, et al., 2019. Long non-coding RNAs in oral squamous cell carcinoma: biologic function, mechanisms and clinical implications. Mol Cancer, 18:102. https://doi.org/10.1186/s12943-019-1021-3
Zhang QZ, Shi SH, Yen Y, et al., 2010. A subpopulation of CD133+ cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Cancer Lett, 289(2):151–160. https://doi.org/10.1016/j.canlet.2009.08.010
Zhao XY, Lu H, Sun Y, et al., 2020. Prognostic value of octamer binding transcription factor 4 for patients with solid tumors: a meta-analysis. Medicine (Baltimore), 99(42):e22804. https://doi.org/10.1097/MD.0000000000022804
Acknowledgments
This work was supported by the Health Commission of Zhejiang Province (No. 2022RC027), China. We also thank Home for Researchers (https://www.home-for-researchers.com) for drawing assistance.
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Yuwei DAI contributed to the conception of the study; Ziqiong WU and Yitong CHEN contributed significantly to analysis and manuscript preparation; Xinjian YE performed the data analysis and wrote the manuscript; Chaowei WANG provided ideas and financial support for the review; Huiyong ZHU helped perform the analysis with constructive discussions and provided substantive guidance on the paper’s ideas and the entire writing process. All authors have read and approved the final manuscript.
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Yuwei DAI, Ziqiong WU, Yitong CHEN, Xinjian YE, Chaowei WANG, and Huiyong ZHU declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Dai, Y., Wu, Z., Chen, Y. et al. OCT4’s role and mechanism underlying oral squamous cell carcinoma. J. Zhejiang Univ. Sci. B 24, 796–806 (2023). https://doi.org/10.1631/jzus.B2200602
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DOI: https://doi.org/10.1631/jzus.B2200602
Key words
- Cancer stem cell (CSC)
- Octamer-binding transcription factor 4 (OCT4)
- Oral squamous cell carcinoma (OSCC)
- Prognosis
- Signaling pathway