Tumor necrosis factor α induces epithelial-mesenchymal transition and promotes metastasis via NF-κB signaling pathway-mediated TWIST expression in hypopharyngeal cancer

Yu,Liang; Mu,Yakui; Sa,Na; Wang,Haibo; Xu,Wei

doi:10.3892/or.2013.2841

Tumor necrosis factor α induces epithelial-mesenchymal transition and promotes metastasis via NF-κB signaling pathway-mediated TWIST expression in hypopharyngeal cancer

Authors:
- Liang Yu
- Yakui Mu
- Na Sa
- Haibo Wang
- Wei Xu
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Affiliations: Department of Otolaryngology - Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: November 11, 2013 https://doi.org/10.3892/or.2013.2841
Pages: 321-327

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Abstract

Epithelial-mesenchymal transition (EMT) is an important mechanism in cancer metastasis. Tumor necrosis factor α (TNFα) can induce cancer invasion and metastasis associated with EMT. However, the underlying mechanisms are not entirely clear. Therefore, we investigated whether TNFα has an effect on EMT and invasion and metastasis in human hypopharyngeal cancer FaDu cells, and further explored the potential mechanisms. In the present study, we demonstrated that TNFα induced EMT in FaDu cells and promoted FaDu cell migration and invasion. TNFα-induced EMT was characterized by a change from well organized cell-cell adhesion and cell polarity to loss of cell-cell contacts, cell scattering and increased expression of vimentin and N-cadherin accompanied by a decrease in E-cadherin. Furthermore, we found that p65 translocated to the nucleus after TNFα stimulation and increased the nuclear expression of TWIST. We demonstrated that TNFα treatment also increased the expression of TWIST by activating the NF-κB signaling pathway. While p65 was inhibited by siRNA-65 or BAY11-7082 (inhibitor of NF-κB), TWIST expression was also decreased. Therefore, we conclude that TNFα induces EMT and promotes metastasis via NF-κB signaling pathway-mediated TWIST expression in hypopharyngeal cancer.

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1	Shacter E and Weitzman SA: Chronic inflammation and cancer. Oncology. 16:217–226. 2292002.
2	Balkwill F: Tumour necrosis factor and cancer. Nat Rev Cancer. 9:361–371. 2009. View Article : Google Scholar
3	Karin M and Greten FR: NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 5:749–759. 2005.
4	Luo JL, Kamata H and Karin M: IKK/NF-κB signaling: balancing life and death - a new approach to cancer therapy. J Clin Invest. 115:2625–2632. 2005.
5	Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI
6	Huber MA, Kraut N and Beug H: Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 17:548–558. 2005. View Article : Google Scholar : PubMed/NCBI
7	Kang Y and Massagué J: Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 118:277–279. 2004. View Article : Google Scholar : PubMed/NCBI
8	Yu L, Lu S, Tian J, et al: TWIST expression in hypopharyngeal cancer and the mechanism of TWIST-induced promotion of metastasis. Oncol Rep. 27:416–422. 2012.PubMed/NCBI
9	Yu L, Li HZ, Lu SM, et al: Down-regulation of TWIST decreases migration and invasion of laryngeal carcinoma Hep-2 cells by regulating the E-cadherin, N-cadherin expression. J Cancer Res Clin Oncol. 137:1487–1493. 2011. View Article : Google Scholar : PubMed/NCBI
10	Wang H, Wang HS, Zhou BH, et al: Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of Snail in colorectal cancer. PLoS One. 8:e566642013.
11	Techasen A, Namwat N, Loilome W, et al: Tumor necrosis factor-α (TNF-α) stimulates the epithelial-mesenchymal transition regulator Snail in cholangiocarcinoma. Med Oncol. 29:3083–3091. 2012.
12	Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM and Zhou BP: Stabilization of Snail by NF-κB is required for inflammation-induced cell migration and invasion. Cancer Cell. 15:416–428. 2009.
13	Wu ST, Sun GH, Hsu CY, et al: Tumor necrosis factor-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a nuclear factor κB-independent mechanism. Exp Biol Med. 236:1022–1029. 2011.
14	Smith RB, Apostolakis LW, Karnell LH, et al: National Cancer Data Base report on osteosarcoma of the head and neck. Cancer. 98:1670–1680. 2003. View Article : Google Scholar : PubMed/NCBI
15	Lefebvre JL, Castelain B, De la Torre JC, Delobelle-Deroide A and Vankemmel B: Lymph node invasion in hypopharynx and lateral epilarynx carcinoma: a prognostic factor. Head Neck Surg. 10:14–18. 1987. View Article : Google Scholar : PubMed/NCBI
16	Eccles SA and Welch DR: Metastasis: recent discoveries and novel treatment strategies. Lancet. 369:1742–1757. 2007. View Article : Google Scholar : PubMed/NCBI
17	Yu L, Li HZ, Lu SM, et al: Alteration in TWIST expression: possible role in paclitaxel-induced apoptosis in human laryngeal carcinoma Hep-2 cell line. Croat Med J. 50:536–542. 2009. View Article : Google Scholar : PubMed/NCBI
18	Bates RC and Mercurio AM: Tumor necrosis factor-α stimulates the epithelial-to-mesenchymal transition of human colonic organoids. Mol Biol Cell. 14:1790–1800. 2003.
19	Takahashi E, Nagano O, Ishimoto T, et al: Tumor necrosis factor-α regulates transforming growth factor-β-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction. J Biol Chem. 285:4060–4073. 2010.
20	Balkwill F: Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev. 13:135–141. 2002. View Article : Google Scholar : PubMed/NCBI
21	Lee SO, Lou W, Hou M, de Miguel F, Gerber L and Gao AC: Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells. Clin Cancer Res. 9:370–376. 2003.PubMed/NCBI
22	Yamauchi Y, Kohyama T, Takizawa H, et al: Tumor necrosis factor-α enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-β1. Exp Lung Res. 36:12–24. 2010.
23	Drake JM, Strohbehn G, Bair TB, Moreland JG and Henry MD: ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells. Mol Biol Cell. 20:2207–2217. 2009. View Article : Google Scholar : PubMed/NCBI
24	Yang J, Mani SA, Donaher JL, et al: Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 117:927–939. 2004. View Article : Google Scholar : PubMed/NCBI
25	Peinado H, Olmeda D and Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 7:415–428. 2007. View Article : Google Scholar : PubMed/NCBI
26	Li CW, Xia W, Huo L, et al: Epithelial-mesenchymal transition induced by TNF-α requires NF-κB-mediated transcriptional upregulation of Twist1. Cancer Res. 72:1290–1300. 2012.
27	Chua HL, Bhat-Nakshatri P, Clare SE, Morimiya A, Badve S and Nakshatri H: NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. Oncogene. 26:711–724. 2007.
28	Min C, Eddy SF, Sherr DH and Sonenshein GE: NF-κB and epithelial to mesenchymal transition of cancer. J Cell Biochem. 104:733–744. 2008.
29	Kaisho T, Takeda K, Tsujimura T, et al: IκB kinase α is essential for mature B cell development and function. J Exp Med. 193:417–426. 2001.
30	Storci G, Sansone P, Mari S, et al: TNFalpha up-regulates SLUG via the NF-kappaB/HIF1alpha axis, which imparts breast cancer cells with a stem cell-like phenotype. J Cell Physiol. 225:682–691. 2010. View Article : Google Scholar : PubMed/NCBI