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Article

Notch signaling induces EMT in OSCC cell lines in a hypoxic environment

  • Authors:
    • Takayuki Ishida
    • Hiroshi Hijioka
    • Kenichi Kume
    • Akihiko Miyawaki
    • Norifumi Nakamura
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan, Department of Clinical Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Yahata-nishi-ku, Kitakyushu 807-8555, Japan
  • Pages: 1201-1206
    |
    Published online on: August 28, 2013
       https://doi.org/10.3892/ol.2013.1549
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Abstract

Epithelial‑mesenchymal transition (EMT) is an early step in the acquisition of invasiveness by malignant tumors. It has been clarified that the tumor microenvironment affects malignancy in a number of different carcinomas, in particular, that a hypoxic environment induces EMT. Activation of Notch signaling induces EMT, but it remains unclear how the Notch pathway is involved in oral squamous cell carcinoma (OSCC) under hypoxia. Three OSCC cell lines were cultured for examination under hypoxic (1% O2) and normoxic (21% O2) conditions. Expression of E‑cadherin was investigated as a hallmark of EMT by immunohistochemical examination. Cell motility and invasion were examined by wound‑healing and invasion assays, respectively. The expression of Notch pathway molecules was analyzed by qPCR. Hypoxia increased the mRNA expression of Notch receptors, ligands and target genes, and Snail. Hypoxia decreased the expression of E‑cadherin, and increased the motility and invasiveness of OSCC cell lines. γ‑secretase inhibitor, a Notch‑specific inhibitor, prevented these effects caused by h-ypoxia. These findings suggest that hypoxia induces EMT in OSCC cell lines via activation of Notch signaling, and inhibition of the Notch signaling pathway to suppress EMT may be a useful approach for the treatment of OSCC.
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1 

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar

2 

Kademani D, Bell RB, Bagheri S, Holmgren E, Dierks E, Potter B and Homer L: Prognostic factors in intraoral squamous cell carcinoma: the influence of histologic grade. J Oral Maxillofac Surg. 63:1599–1605. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Weinberg RA: Twisted epithelial-mesenchymal transition blocks senescence. Nat Cell Biol. 10:1021–1023. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Yang MH, Wu MZ, Chiou SH, et al: Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol. 10:295–305. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Cannito S, Novo E, Compagnone A, et al: Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis. 29:2267–2278. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Leong KG, Niessen K, Kulic I, et al: Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 204:2935–2948. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Miele L: Notch signaling. Clin Cancer Res. 12:1074–1079. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Wang Z, Zhang Y, Li Y, Banerjee S, Liao J and Sarkar FH: Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther. 5:483–493. 2006. View Article : Google Scholar

9 

Chen J, Imanaka N, Chen J and Griffin JD: Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer. 102:351–360. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Pietras A, von Stedingk K, Lindgren D, Påhlman S and Axelson H: JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation. Mol Cancer Res. 9:626–636. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Bedogni B, Warneke JA, Nickoloff BJ, Giaccia AJ and Powell MB: Notch1 is an effector of Akt and hypoxia in melanoma development. J Clin Invest. 118:36602008. View Article : Google Scholar : PubMed/NCBI

12 

Jiang YG, Luo Y, He DL, et al: Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha. Int J Urol. 14:1034–1039. 2007. View Article : Google Scholar

13 

Chambers AF, Groom AC and MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2:563–572. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Ansieau S, Bastid J, Doreau AS, et al: Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell. 14:79–89. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Gavert N, Conacci-Sorrell M, Gast D, et al: L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol. 168:633–642. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Hlubek F, Spaderna S, Jung A, et al: β-catenin activates a coordinated expression of the proinvasive factors laminin-5 γ2 chain and MT1-MMP in colorectal carcinomas. Int J cancer. 108:321–326. 2004.

17 

Brizel DM, Scully SP, Harrelson JM, et al: Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res. 56:941–943. 1996.PubMed/NCBI

18 

Hockel M, Schlenger K, Aral B and Mitze M: Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res. 56:4509–4515. 1996.PubMed/NCBI

19 

Fyles A, Milosevic M, Wong R, et al: Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol. 48:149–156. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Hill RP, Marie-Egyptienne DT and Hedley DW: Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol. 19:106–111. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Howard JD, Lu B and Chung CH: Therapeutic targets in head and neck squamous cell carcinoma: Identification, evaluation, and clinical translation. Oral Oncol. 48:10–17. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Agrawal N, Frederick MJ, Pickering CR, et al: Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 333:1154–1157. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Stransky N, Egloff AM, Tward AD, et al: The mutational landscape of head and neck squamous cell carcinoma. Science. 333:1157–1160. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Hijioka H, Setoguchi T, Miyawaki, et al: Upregulation of Notch pathway molecules in oral squamous cell carcinoma. Int J Oncol. 36:817–822. 2010.PubMed/NCBI

25 

Weijzen S, Rizzo P, Braid M, et al: Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med. 8:979–986. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Santagata S, Demichelis F, Riva A, et al: JAGGED1 expression is associated with prostate cancer metastasis and recurrence. Cancer Res. 64:6854–6857. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Dickson BC, Mulligan AM, Zhang H, et al: High-level JAG1 mRNA and protein predict poor outcome in breast cancer. Mod Pathol. 20:685–693. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Lin JT, Chen MK, Yeh KT, et al: Association of high levels of Jagged-1 and Notch-1 expression with poor prognosis in head and neck cancer. Ann Surg Oncol. 17:2976–2983. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Zhang TH, Liu HC, Zhu LJ, et al: Activation of Notch signaling in human tongue carcinoma. J Oral Pathol Med. 40:37–45. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Zavadil J, Cermak L, Soto-Nieves N and Böttinger EP: Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J. 23:1155–1165. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Sahlgren C, Gustafsson MV, Jin S, Poellinger L and Lendahl U: Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA. 105:6392–6397. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW and Semenza GL: Expression of hypoxia-inducible factor 1alpha in brain tumors: association with angiogenesis, invasion, and progression. Cancer. 88:2606–2618. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Harris AL: Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–47. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Schindl M, Schoppmann SF, Samonigg H, et al: Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin Cancer Res. 8:1831–1837. 2002.PubMed/NCBI

35 

Gupta GP and Massagué J: Cancer metastasis: building a framework. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Perl AK, Wilgenbus P, Dahl U, Semb H and Christofori G: A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 392:190–193. 1998. View Article : Google Scholar : PubMed/NCBI

37 

Moody SE, Perez D, Pan TC, et al: The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 8:197–209. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Erler JT, Bennewith KL, Nicolau M, et al: Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 440:1222–1226. 2006. View Article : Google Scholar : PubMed/NCBI

39 

Pouysségur J, Dayan F and Mazure NM: Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 441:437–443. 2006.PubMed/NCBI

40 

Timmerman LA, Grego-Bessa J, Raya A, et al: Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 18:99–115. 2004. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Ishida T, Hijioka H, Kume K, Miyawaki A and Nakamura N: Notch signaling induces EMT in OSCC cell lines in a hypoxic environment. Oncol Lett 6: 1201-1206, 2013.
APA
Ishida, T., Hijioka, H., Kume, K., Miyawaki, A., & Nakamura, N. (2013). Notch signaling induces EMT in OSCC cell lines in a hypoxic environment. Oncology Letters, 6, 1201-1206. https://doi.org/10.3892/ol.2013.1549
MLA
Ishida, T., Hijioka, H., Kume, K., Miyawaki, A., Nakamura, N."Notch signaling induces EMT in OSCC cell lines in a hypoxic environment". Oncology Letters 6.5 (2013): 1201-1206.
Chicago
Ishida, T., Hijioka, H., Kume, K., Miyawaki, A., Nakamura, N."Notch signaling induces EMT in OSCC cell lines in a hypoxic environment". Oncology Letters 6, no. 5 (2013): 1201-1206. https://doi.org/10.3892/ol.2013.1549
Copy and paste a formatted citation
x
Spandidos Publications style
Ishida T, Hijioka H, Kume K, Miyawaki A and Nakamura N: Notch signaling induces EMT in OSCC cell lines in a hypoxic environment. Oncol Lett 6: 1201-1206, 2013.
APA
Ishida, T., Hijioka, H., Kume, K., Miyawaki, A., & Nakamura, N. (2013). Notch signaling induces EMT in OSCC cell lines in a hypoxic environment. Oncology Letters, 6, 1201-1206. https://doi.org/10.3892/ol.2013.1549
MLA
Ishida, T., Hijioka, H., Kume, K., Miyawaki, A., Nakamura, N."Notch signaling induces EMT in OSCC cell lines in a hypoxic environment". Oncology Letters 6.5 (2013): 1201-1206.
Chicago
Ishida, T., Hijioka, H., Kume, K., Miyawaki, A., Nakamura, N."Notch signaling induces EMT in OSCC cell lines in a hypoxic environment". Oncology Letters 6, no. 5 (2013): 1201-1206. https://doi.org/10.3892/ol.2013.1549
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