Twist1 regulates the epithelial–mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma
Tóm tắt
Expression of the oncogene Twist1 is correlated with tumor development and metastasis. Recent studies have suggested that the epithelial-to-mesenchymal transition (EMT) is necessary for tumor progression and metastases. Little is known concerning the role of Twist1 and EMT in thyroid cancer. In the present work, the expression levels of Twist1 and one marker of EMT, vimentin, were measured in papillary thyroid carcinoma (PTC). The results showed Twist1 expression to be correlated only with cancer lymph node metastases (P = 0.004) and not with other clinicopathological indicators. Moreover, Twist1 expression was positively correlated with the expression of vimentin (r = 0.408, P = 0.003). In vitro studies further indicated that reducing Twist1 expression using short hairpin RNA against Twist1 can decrease the invasive and metastatic properties of PTC cells and that the down-regulation of Twist1 can reverse EMT by increasing the expression of E-cadherin and down-regulating the expression of vimentin in the PTC cell line IHH-4. To investigate the effects on Twist1, the PTC cell lines TPC-1 and BCPAP were treated with TNF-α, resulting in Twist1 up-regulation that was dependent on NF-κB activation. After the inhibition of NF-κB activity with Bay11-7082, the Twist1 mRNA and protein levels could not be increased. The decline in the Twist1 mRNA and protein levels rendered the cancer cells less invasive. Thus, we conclude that Twist1 plays an important role in the EMT of PTC via the NF-κB pathway.
Tài liệu tham khảo
J. Yang, S.A. Mani, J.L. Donaher, S. Ramaswamy, R.A. Itzykson, C. Come, P. Savagner, I. Gitelman, A. Richardson, R.A. Weinberg, Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117, 927–939 (2004)
R. Kalluri, R.A. Weinberg, The basics of epithelial-mesenchymal transition. J. Clin. Investig. 119, 1420–1428 (2009)
S.J. Grille, A. Bellacosa, J. Upson, A.J. Klein-Szanto, F. van Roy, W. Lee-Kwon, M. Donowitz, P.N. Tsichlis, L. Larue, The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 63, 2172–2178 (2003)
R.C. Bates, A.M. Mercurio, The epithelial–mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol. Ther. 4, 365–370 (2005)
C. Xue, D. Plieth, C. Venkov, C. Xu, E.G. Neilson, The gatekeeper effect of epithelial–mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Res. 63, 3386–3394 (2003)
S. Nakajima, R. Doi, E. Toyoda, S. Tsuji, M. Wada, M. Koizumi et al., N-cadherin expression and epithelial–mesenchymal transition in pancreatic carcinoma. Clin. Cancer Res. 15, 4125–4133 (2004)
J.E. Visvader, G.J. Lindeman, Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat. Rev. Cancer 8, 755–768 (2008)
B. Aktas, M. Tewes, T. Fehm, S. Hauch, R. Kimmig, S. Kasimir-Bauer, Stem cell and epithelial–mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 11, R46 (2009)
J. Comijn, G. Berx, P. Vermassen, K. Verschueren, L. van Grunsven, E. Bruyneel, M. Mareel, D. Huylebroeck, F. van Roy, The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol. Cell 7, 1267–1278 (2001)
M.H. Yang, M.Z. Wu, S.H. Chiou et al., Direct regula-tion of TWIST by HIF-1alpha promotes metastasis. Nat. Cell Biol. 10, 295–305 (2008)
M.H. Yang, K.J. Wu, TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle 7, 2090–2096 (2013)
H. Wang, H.S. Wang, B.H. Zhou et al., Epithelial–mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PLoS ONE 8, e56664 (2013)
L. Yu, Y. Mu, N. Sa, H. Wang, W. Xu, Tumor necrosis factor α induces epithelial–mesenchymal transition and promotes metastasis via NF-κB signaling pathway-mediated TWIST expression in hypopharyngeal cancer. Oncol. Rep. 31, 321–327 (2014)
Y. Wu, B.P. Zhou, TNF-α/NF-κB/Snail pathway in cancer cell migration and invasion. Br. J. Cancer 102, 639–644 (2010)
C.W. Li, W. Xia, L. Huo et al., Epithelial–mesenchymal transition induced by TNF-α requires NF-κB-mediated transcriptional upregulation of Twist1. Cancer Res. 72, 1290–1300 (2012)
S. Ansieau, J. Bastid, A. Doreau 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)
G. Yin, R. Chen, A.B. Alvero et al., TWISTing stemness, inflammation, and proliferation of epithelial ovarian cancer cells through MIR199A2/214. Oncogene 29, 3545–3553 (2010)
Y. Soini, H. Tuhkanen, R. Sironen, I. Virtanen, V. Kataja, P. Auvinen, A. Mannermaa, V.M. Kosma, Transcription factors zeb1, twist and snai1 in breast carcinoma. BMC Cancer (2011). doi:10.1186/1471-2407-11-73
K. Ohba, Y. Miyata, T. Matsuo et al., High expression of Twist is associated with tumor aggressiveness and poor prognosis in patients with renal cell carcinoma. Int. J. Clin. Exp. Pathol. 7, 3158–3165 (2014)
P. Salerno, G. Garcia-Rostan, S. Piccinin et al., TWIST1 plays a pleiotropic role in determining the anaplastic thyroid cancer phenotype. J. Clin. Endocrinol. Metab. 96, E772–E781 (2011)
D. Buehler, H. Hardin, W. Shan et al., Expression of epithelial -mesenchymal transition regulators SNAI2 and TWIST1 in thyroid carcinomas. Mod. Pathol. 26, 54–61 (2013)
N. Wang, H.J. Luo, G.B. Yin, C.R. Dong, M. Xu, G.G. Chen, Z.M. Liu, Overexpression of HIF-2α, TWIST, and CXCR4 Is associated with lymph node metastasis in papillary thyroid carcinoma. Clin. Dev. Immunol. 2013, 589423 (2013)
V. Vasko, A.V. Espinosa, W. Scouten et al., Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion. Proc Natl Acad Sci USA. 104, 2803–2808 (2007)
J.A. Knauf, M.A. Sartor, M. Medvedovic et al., Progression of BRAF-induced thyroid cancer is associated with epithelial–mesenchymal transition requiring concomitant MAP kinase and TGFβ signaling. Oncogene 30, 3153–3162 (2011)
D.S. Micalizzi, S.M. Farabaugh, H.L. Ford, Epithelial–mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol. Neoplasia. 15, 117–134 (2010)
J. Gotzmann, M. Mikula, A. Eger et al., Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis. Mutat. Res. 566, 9–20 (2004)
D. Hanahan, R.A. Weinberg, The hallmarks of cancer. Cell 100, 57–70 (2000)
K.H. Cho, K.J. Jeong, S.C. Shin, STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion. Cancer Lett. 336, 167–173 (2013)
K. Satoh, S. Hamada, K. Kimura et al., Up-regulation of MSX2 enhances the malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells. Am. J. Pathol. 172, 926–939 (2008)
K. Pallier, A. Cessot, J.F. Côté et al., TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma. PLoS ONE 7, e29954 (2012)
L.P. Hui, S.Y. Zhang, X.J. Dong et al., Prognostic significance of twist and n-cadherin expression in NSCLC. PLoS ONE 8, e62171 (2013)
Y. Jing, Z. Han, Y. Liu et al., Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial–mesenchymal transition. PLoS ONE 7, e43272 (2012)
S.T. Wu, G.H. Sun, C.Y. Hsu et al., Tumor necrosis factor-α induces epithelial–mesenchymal transition of renal cell carcinoma cells via a nuclear factor kappa B-independent mechanism. Exp. Biol. Med. (Maywood). 236, 1022–1029 (2011)
A. Shiozaki, X.H. Bai, G. Shen-Tu et al., Claudin 1 mediates TNFα-induced gene expression and cell migration in human lung carcinoma cells. PLoS ONE 7, e38049 (2012)
A. Banerjee, Z.S. Wu, P.X. Qian et al., ARTEMIN synergizes with TWIST1 to promote metastasis and poor survival outcome in patients with ER negative mammary carcinoma. Breast Cancer Res. 13, R112 (2011)
M.B. Weiss, E.V. Abel, M.M. Mayberry et al., TWIST1 is an ERK1/2 effector that promotes invasion and regulates MMP-1 expression in human melanoma cells. Cancer Res. 72, 6382–6392 (2012)
S.B. Pakala, S.K. Rayala, R.A. Wang et al., MTA1 promotes STAT3 transcription and pulmonary metastasis in breast cancer. Cancer Res. 73, 3761–3770 (2013)