C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer
C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer
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DOI：
10.1002/path.2508
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发表时间：
2009-05-01
影响因子：
7.3
通讯作者：
Ilyas, Mohammad
中科院分区：
文献类型：
--
作者：
Albasri, Abdulkader;Seth, Rashmi;Ilyas, Mohammad
张力蛋白基因家族编码被认为调节整联蛋白功能的蛋白质。C-terminal Tensin-like（CTEN）是Tensin基因家族的一员，其缺乏N-末端肌动蛋白结合结构域。据报道，Cten具有致癌和肿瘤抑制功能。我们研究了Cten在结直肠癌（CRC）中可能发挥的作用。通过定量RT-PCR，与正常粘膜相比，CTEN在62%的细胞系和69%的肿瘤中上调（即>两倍增加），与CTEN是可能的致癌基因一致。用Cten表达载体稳定转染HCT 116和SW 480（具有低内源性Cten表达的CRC细胞系）在两种细胞系中得到相同的结果。强制的Cten表达不引起细胞数量的变化，尽管它可能赋予对星形孢菌素诱导的细胞凋亡的抗性（p < 0.005）。Cten还诱导肿瘤细胞中的上皮-间充质转化（EMT），伴随着细胞迁移（transwell迁移和细胞创伤测定，分别为p < 0.001和p < 0.05）和细胞侵袭（通过基质胶的侵袭，p < 0.001）的显著增加。鉴于观察到的EMT，我们研究了E-钙粘蛋白的水平。Cten诱导与E-钙粘蛋白蛋白表达的减少有关，但与E-钙粘蛋白mRNA水平无关。这些数据表明，CTEN是CRC中的致癌基因，其刺激EMT、细胞迁移和侵袭，因此可能在肿瘤侵袭/扩散中起作用。此外，Cten诱导与E-钙粘蛋白的转录后抑制相关。版权所有（C）2008大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
The Tensin gene family encodes proteins thought to modulate integrin function. C-terminal Tensin-like (CTEN) is a member of the Tensin gene family which lacks the N-terminus actin-binding domain. Cten is reported to have both oncogenic and tumour-suppressor functions. We investigated the role that Cten may play in colorectal cancer (CRC). By quantitative RT-PCR CTEN is up-regulated (i.e. > two-fold increase) in 62% of cell lines and 69% of tumours compared with normal mucosa, consistent with CTEN being a possible oncogene. Stable transfection of HCT116 and SW480 (CRC cell lines with low endogenous Cten expression) with a Cten expression vector gave identical results in both cell lines. Forced Cten expression did not cause change in cell numbers, although it (lid confer resistance to staurosporine-induced apoptosis (p < 0.005). Cten also induced epitheliaL-mesenchymal transition (EMT) in tumour cells accompanied by a significant increase in both cell migration (transwell migration and cell wounding assays, p < 0.001 and p < 0.05, respectively) and cell invasion (invasion through Matrigel, p < 0.001). Given the observed EMT, we investigated the levels of E-cadherin. Cten induction was associated with a reduction in E-cadherin protein expression but not levels of E-cadherin mRNA. These data suggest that CTEN is an oncogene in CRC which stimulates EMT, cell migration and invasion and may therefore have a role in tumour invasion/spread. Furthermore, Cten induction is associated with post-transcriptional repression of E-cadherin. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.