Esra AYDEMİR, Ezgi KAŞIKCI, Ömer Faruk BAYRAK, Fikrettin ŞAHİN

The effect of TWIST silencing in metastatic chordoma cells

Chordoma is a slowly growing and invasive bone tumor with a tendency to metastasize locally in advanced stages. It is essential to discover new therapeutics that target genes involved in the metastasis of chordoma. Epithelial-mesenchymal transition (EMT) might robustly influence the metastasis of a tumor bulk. To our knowledge, this is the first time to show that EMT might have a role in chordoma metastasis. In this study, we aim to investigate the possible role of Twist, a key player transcription factor of EMT, in chordoma metastasis. The TWIST gene was silenced by short hairpins in chordoma cell line MUG-Chor1 and effects on metastasis were investigated by wound healing/gap closure and invasion assays. Twist-silenced MUG-Chor1 cells were found to be less migratory and less invasive when compared to the negative control. This study indicates that Twist might have a role in metastatic chordoma cells.

Keywords:

Cancer, epithelial-mesenchymal transition, chordoma, twist,

PDF

___

Abrahams A, Parker MI, Prince S (2010). The T-box transcription factor Tbx2: its role in development and possible implication in cancer. IUBMB Life 62: 92-102.
Bates RC, Mercurio AM (2005). The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther 4: 365-370.
Bergh P, Kindblom LG, Gunterberg B, Remotti F, Ryd W, Meis- Kindblom JM (2000). Prognostic factors in chordoma of the sacrum and mobile spine - A study of 39 patients. Cancer 88: 2122-2134.
Chambers PW, Schwinn CP (1979). Chordoma. A clinicopathologic study of metastasis. Am J Clin Pathol 72: 765-776.
Chen ZF, Behringer RR (1995). Twist is required in head mesenchyme for cranial neural-tube morphogenesis. Gene Dev 9: 686-699.
Cheng GZ, Zhang W, Wang LH (2008). Regulation of cancer cell survival, migration, and invasion by Twist: AKT2 comes to interplay. Cancer Res 68: 957-960.
Croset M, Goehrig D, Frackowiak A, Bonnelye E, Ansieau S, Puisieux A, Clezardin P (2014). TWIST1 expression in breast cancer cells facilitates bone metastasis formation. J Bone Miner Res 29: 1886-1899.
Du WL, Fang Q, Chen Y, Teng JW, Xiao YS, Xie P, Jin B, Wang JQ (2017). Effect of silencing the T-Box transcription factor TBX2 in prostate cancer PC3 and LNCaP cells. Mol Med Rep 16: 6050- 6058.
Eccles SA, Welch DR (2007). Metastasis: recent discoveries and novel treatment strategies. Lancet 369: 1742-1757.
Fu J, Qin L, He T, Qin J, Hong J, Wong J, Liao L, Xu J (2011). The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis. Cell Res 21: 275-289.
Hong J, Zhou J, Fu J, He T, Qin J, Wang L, Liao L, Xu J (2011). Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. Cancer Res 71: 3980-3990.
Huber MA, Kraut N, Beug H (2005). Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 17: 548-558.
Karamchandani J, Wu MY, Das S, Vogel H, Muller P, Cusimano M, Montanera W, Kovacs K (2013). Highly proliferative sellar chordoma with unusually rapid recurrence. Neuropathology 33: 424-430.
Kwok WK, Ling MT, Lee TW, Lau TC, Zhou C, Zhang X, Chua CW, Chan KW, Chan FL, Glackin C et al. (2005). Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target. Cancer Res 65: 5153-5162.
Liu GL, Yang HJ, Liu T, Lin YZ (2014). Expression and significance of E-cadherin, N-cadherin, transforming growth factor-beta 1 and Twist in prostate cancer. Asian Pac J Trop Med 7: 76-82.
Markwalder TM, Markwalder RV, Robert JL, Krneta A (1979). Metastatic chordoma. Surg Neurol 12: 473-478.
Matsuo N, Shiraha H, Fujikawa T, Takaoka N, Ueda N, Tanaka S, Nishina S, Nakanishi Y, Uemura M, Takaki A et al. (2009). Twist expression promotes migration and invasion in hepatocellular carcinoma. BMC Cancer 9: 240.
McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM (2001). Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Cause Control 12: 1-11.
McPherson CM, Suki D, McCutcheon IE, Gokaslan ZL, Rhines LD, Mendel E (2006). Metastatic disease from spinal chordoma: a 10-year experience. J Neurosurg-Spine 5: 277-280.
Oakley GJ, Fuhrer K, Seethala RR (2008). Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Modern Pathol 21: 1461-1469.
Rinner B, Froehlich EV, Buerger K, Knausz H, Lohberger B, Scheipl S, Fischer C, Leithner A, Guelly C, Trajanoski S et al. (2012). Establishment and detailed functional and molecular genetic characterisation of a novel sacral chordoma cell line, MUG- Chor1. Int J Oncol 40: 443-451.
Thiery JP (2002). Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2: 442-454.
Thiery JP (2003). Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 15: 740-746.
Vanderheijden C (2014). Chordoma and its embryonic determinants. Marble Research Paper 308: 150-159.
Vergara G, Belinchon B, Valcarcel F, Veiras M, Zapata I, de la Torre A (2008). Metastatic disease from chordoma. Clin Transl Oncol 10: 517-521.
Vesuna F, van Diest P, Chen JH, Raman V (2008). Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Bioph Res Co 367: 235-241.
Wang B, Lindley LE, Fernandez-Vega V, Rieger ME, Sims AH, Briegel KJ (2012). The T box transcription factor TBX2 promotes epithelial-mesenchymal transition and invasion of normal and malignant breast epithelial cells. PLoS One 7: e41355.
Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117: 927-939.
Yang J, Mani SA, Weinberg RA (2006). Exploring a new twist on tumor metastasis. Cancer Res 66: 4549-4552.
Yang MH, Chen CL, Chau GY, Chiou SH, Su CW, Chou TY, Peng WL, Wu JC (2009). Comprehensive analysis of the independent effect of Twist and Snail in promoting metastasis of hepatocellular carcinoma. Hepatology 50: 1464-1474.
Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ (2009). T (Brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet 41: 1176-1178.
Yang Z, Zhang X, Gang H, Li X, Li Z, Wang T, Han J, Luo T, Wen F, Wu X (2007). Up-regulation of gastric cancer cell invasion by Twist is accompanied by N-cadherin and fibronectin expression. Biochem Bioph Res Co 358: 925-930.
Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M, Hung MC (2004). Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol 6: 931-940.