Asiri Abdulaziz, Raposo Teresa Pereira, Alfahed Abdulaziz, Ilyas Mohammad
Division of Cancer and Stem Cells, Queen's Medical Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Nottingham Molecular Pathology Node, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Int J Exp Pathol. 2018 Dec;99(6):323-330. doi: 10.1111/iep.12300. Epub 2019 Jan 15.
Cten (C-terminal tensin-like) is a member of the tensin protein family found in complex with integrins at focal adhesions. It promotes epithelial-mesenchymal transition (EMT) and cell motility. The precise mechanisms regulating Cten are unknown, although we and others have shown that Cten could be under the regulation of several cytokines and growth factors. Since transforming growth factor beta 1 (TGF-β1) regulates integrin function and promotes EMT/cell motility, we were prompted to investigate whether TGF-β1 induces EMT and cell motility through Cten signalling in colorectal cancer. TGF-β1 signalling was modulated by either stimulation with TGF-β1 or knockdown of TGF-β1 in the CRC cell lines SW620 and HCT116. The effect of this modulation on expression of Cten, EMT markers and on cellular function was tested. The role of Cten as a direct mediator of TGF-β1 signalling was investigated in a CRC cell line in which the Cten gene had been deleted (SW620 ). When TGF-β1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers (Snail, Rock, N-cadherin, Src). Cell migration and cell invasion were significantly increased following TGF-β1 stimulation and lost by TGF-β1 knockdown. TGF-β1 stimulation of the SW620 cell line resulted in selective loss of the effect of TGF-β1 signalling pathway on EMT and cell motility while the stimulatory effect on cell proliferation was retained. These data suggested Cten may play an essential role in mediating TGF-β1-induced EMT and cell motility and may therefore play a role in metastasis in CRC.
Cten（C末端张力蛋白样蛋白）是张力蛋白家族的成员，在粘着斑处与整合素形成复合物。它促进上皮-间质转化（EMT）和细胞迁移。尽管我们和其他人已经表明Cten可能受几种细胞因子和生长因子的调控，但其精确的调控机制尚不清楚。由于转化生长因子β1（TGF-β1）调节整合素功能并促进EMT/细胞迁移，我们因此研究TGF-β1是否通过Cten信号通路在结直肠癌中诱导EMT和细胞迁移。在结直肠癌细胞系SW620和HCT116中，通过用TGF-β1刺激或敲低TGF-β1来调节TGF-β1信号通路。测试这种调节对Cten、EMT标志物表达以及细胞功能的影响。在Cten基因已被删除的结直肠癌细胞系（SW620）中研究Cten作为TGF-β1信号直接介导因子的作用。当TGF-β1被刺激或抑制时，分别导致Cten表达和EMT标志物（Snail、Rock、N-钙黏蛋白、Src）的上调和下调。TGF-β1刺激后细胞迁移和细胞侵袭显著增加，而敲低TGF-β1则使其丧失。对SW620细胞系进行TGF-β1刺激导致TGF-β1信号通路对EMT和细胞迁移的作用选择性丧失，而对细胞增殖的刺激作用得以保留。这些数据表明，Cten可能在介导TGF-β1诱导的EMT和细胞迁移中起重要作用，并因此可能在结直肠癌转移中发挥作用。
