FoxM1 Promotes Cell Proliferation, Invasion, and Stem Cell Properties in Nasopharyngeal Carcinoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2018 Nov 13

PMID 30416986

Citations 29

Authors

Weiren Luo

Fei Gao

Siyi Li

Lei Liu

Affiliations

Soon will be listed here.

Abstract

The self-renewal and tumourigenicity of FoxM1 in nasopharyngeal carcinoma (NPC) remain largely unknown. In this study, we attempt to investigate the self-renewal and tumourigenicity of FoxM1 and its clinical significance in nasopharyngeal carcinoma (NPC). Several assays including cell counting Kit-8 (CCK-8) assays, colony formation, flow cytometry, immunofluorescence, tumor spheres, and mice model were used to detect the biological function of FoxM1 in NPC. The association between FoxM1 and clinical pathological features, and stem cell markers was analyzed using immunohistochemistry. High expression of FoxM1 was prominently present in the T4 stages, cancer cells migrating into the stroma and vasculature. Overexpression of FoxM1 enhanced tumor proliferation, cell cycle progression, migration and stress fibers formation . In NPC tissues, FoxM1 correlated significantly with stem cells-related clinical pathological features including late clinical stage, tumor recurrence and distant metastasis. Meanwhile, FoxM1 linked closely with the expression levels of stem cell markers including Nanog, Sox2, and OCT4 in tumor samples, and also promoted the expression of these stemness-related genes . Moreover, FoxM1 conferred the self-renewal properties of cancer cells by increasing side populations (SP) cells and formed larger and more tumor spheres. Importantly, FoxM1 enhanced the ability of tumourigenicity of NPC cell lines in mice xenograft. We demonstrate that FoxM1 greatly induces cancer progression and cancer stem cell (CSC) features in NPC.

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References

Hou Y, Zhu Q, Li Z, Peng Y, Yu X, Yuan B . The FOXM1-ABCC5 axis contributes to paclitaxel resistance in nasopharyngeal carcinoma cells. Cell Death Dis. 2017; 8(3):e2659. PMC: 5386553. DOI: 10.1038/cddis.2017.53. View

Huang P, Li Y, Luo D, Hou X, Zeng T, Li M . Expression of Aurora-B and FOXM1 predict poor survival in patients with nasopharyngeal carcinoma. Strahlenther Onkol. 2015; 191(8):649-55. DOI: 10.1007/s00066-015-0840-4. View

Palla A, Piazzolla D, Alcazar N, Canamero M, Grana O, Gomez-Lopez G . The pluripotency factor NANOG promotes the formation of squamous cell carcinomas. Sci Rep. 2015; 5:10205. PMC: 4437308. DOI: 10.1038/srep10205. View

Lu C, Shieh G, Wang C, Su B, Su Y, Chen Y . Chemotherapeutics-induced Oct4 expression contributes to drug resistance and tumor recurrence in bladder cancer. Oncotarget. 2016; 8(19):30844-30858. PMC: 5458172. DOI: 10.18632/oncotarget.9602. View

Li L, Wu D, Yu Q, Li L, Wu P . Prognostic value of FOXM1 in solid tumors: a systematic review and meta-analysis. Oncotarget. 2017; 8(19):32298-32308. PMC: 5458285. DOI: 10.18632/oncotarget.15764. View

Gao F, Zhang Y, Wang S, Liu Y, Zheng L, Yang J . Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer. Sci Rep. 2014; 4:3963. PMC: 3912485. DOI: 10.1038/srep03963. View

Luo W, Yao K . Molecular characterization and clinical implications of spindle cells in nasopharyngeal carcinoma: a novel molecule-morphology model of tumor progression proposed. PLoS One. 2013; 8(12):e83135. PMC: 3861507. DOI: 10.1371/journal.pone.0083135. View

Luo W, Li S, Peng B, Ye Y, Deng X, Yao K . Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 2013; 8(2):e56324. PMC: 3570418. DOI: 10.1371/journal.pone.0056324. View

Luo W, Li S, Cai L, Yao K . High expression of nuclear Snail, but not cytoplasmic staining, predicts poor survival in nasopharyngeal carcinoma. Ann Surg Oncol. 2012; 19(9):2971-9. DOI: 10.1245/s10434-012-2347-x. View

10.

Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang D . Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res. 2005; 65(14):6207-19. DOI: 10.1158/0008-5472.CAN-05-0592. View

11.

Lam E, Brosens J, Gomes A, Koo C . Forkhead box proteins: tuning forks for transcriptional harmony. Nat Rev Cancer. 2013; 13(7):482-95. DOI: 10.1038/nrc3539. View

12.

Chen H, Yang C, Yu L, Xie L, Hu J, Zeng L . Adenovirus-mediated RNA interference targeting FOXM1 transcription factor suppresses cell proliferation and tumor growth of nasopharyngeal carcinoma. J Gene Med. 2012; 14(4):231-40. DOI: 10.1002/jgm.2614. View

13.

Clevers H . The cancer stem cell: premises, promises and challenges. Nat Med. 2011; 17(3):313-9. DOI: 10.1038/nm.2304. View

14.

Zhang H, Ren C, Yang X, Wang L, Li H, Zhao M . Identification of label-retaining cells in nasopharyngeal epithelia and nasopharyngeal carcinoma tissues. Histochem Cell Biol. 2006; 127(3):347-54. DOI: 10.1007/s00418-006-0251-9. View

15.

Friedl P, Wolf K . Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003; 3(5):362-74. DOI: 10.1038/nrc1075. View

16.

Mackillop W, Ciampi A, Till J, Buick R . A stem cell model of human tumor growth: implications for tumor cell clonogenic assays. J Natl Cancer Inst. 1983; 70(1):9-16. View

17.

Quan M, Wang P, Cui J, Gao Y, Xie K . The roles of FOXM1 in pancreatic stem cells and carcinogenesis. Mol Cancer. 2013; 12:159. PMC: 3924162. DOI: 10.1186/1476-4598-12-159. View

18.

Hamurcu Z, Ashour A, Kahraman N, Ozpolat B . FOXM1 regulates expression of eukaryotic elongation factor 2 kinase and promotes proliferation, invasion and tumorgenesis of human triple negative breast cancer cells. Oncotarget. 2016; 7(13):16619-35. PMC: 4941339. DOI: 10.18632/oncotarget.7672. View

19.

Jiang L, Wang P, Chen L, Chen H . Down-regulation of FoxM1 by thiostrepton or small interfering RNA inhibits proliferation, transformation ability and angiogenesis, and induces apoptosis of nasopharyngeal carcinoma cells. Int J Clin Exp Pathol. 2014; 7(9):5450-60. PMC: 4203158. View

20.

Ben-Porath I, Thomson M, Carey V, Ge R, Bell G, Regev A . An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008; 40(5):499-507. PMC: 2912221. DOI: 10.1038/ng.127. View