Multiple pathways regulate Cten in colorectal cancer without a Tensin switch
Multiple pathways regulate Cten in colorectal cancer without a Tensin switch
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DOI：
10.1111/iep.12154
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发表时间：
2015-12-01
影响因子：
3
通讯作者：
Ilyas, Mohammad
中科院分区：
文献类型：
--
作者：
Thorpe, Hannah;Akhlaq, Maham;Ilyas, Mohammad
CTEN/TNS 4是Tensin基因家族的成员。它定位于粘着斑并诱导细胞运动。尽管我们已经显示结肠和胰腺中的Kras调控，但调节Cten表达的机制尚不清楚。在正常乳腺细胞系中，据报道其通过表皮生长因子受体（EGFR）和STAT 3信号传导上调，并且上调伴随着张力蛋白3（张力蛋白开关）的下调。在这项研究中，我们研究了EGFR和STAT 3信号转导在结肠直肠癌（CRC）中Cten调节中的作用。此外，我们研究了钙蛋白酶-一种与Cten相关的局灶性粘附相关蛋白的调节剂。用表皮生长因子（EGF）刺激CRC细胞系。这导致Cten和Tensin 3蛋白的增加。Kras被敲低，这导致Cten和Tensin 3下调。我们接下来研究了STAT 3信号传导的作用。STAT 3的激活和敲低分别导致Cten的下调和上调。钙蛋白酶的抑制导致Cten和张力蛋白3的上调。由于Cten的调节因子似乎也调节Tensin 3，我们测试了Cten和Tensin 3之间的相互作用。Cten被强制表达或敲低，分别导致Tensin 3的上调和下调。我们得出结论，在CRC中，Cten被EGFR和Kras上调，但被STAT 3下调。我们发现钙蛋白酶可能是Cten的负调节因子，并且不会发生Tensin开关，如果有的话，Cten稳定Tensin 3。
CTEN/TNS4 is a member of the Tensin gene family. It localizes to focal adhesions and induces cell motility. The mechanisms regulating Cten expression are unclear although we have shown regulation by Kras in the colon and pancreas. In normal mammary cell lines, it is reportedly upregulated by epidermal growth factor receptor (EGFR) and STAT3 signalling and upregulation is accompanied by downregulation of Tensin 3 (Tensin switch). In this study, we investigated the roles of EGFR and STAT3 signalling in the regulation of Cten in colorectal cancer (CRC). In addition, we investigated calpain - a regulator of focal adhesion-associated proteins whose relevance to Cten has not been investigated. CRC cell lines were stimulated with epidermal growth factor (EGF). This resulted in an increase in Cten and Tensin 3 protein. Kras was knocked down and this resulted in downregulation of Cten and Tensin 3. We next investigated the role of STAT3 signalling. Activation and knockdown of STAT3 resulted in downregulation and upregulation, respectively, of Cten. Inhibition of calpain resulted in upregulation of both Cten and Tensin 3. As the regulators of Cten also seemed to regulate Tensin 3, we tested the interaction between Cten and Tensin 3. Cten was forcibly expressed or knocked down resulting, respectively, in upregulation and downregulation of Tensin 3. We conclude that in CRC, Cten is upregulated by EGFR and Kras but downregulated by STAT3. We show that calpain may be a negative regulator of Cten and that a Tensin switch does not occur and, if anything, Cten stabilizes Tensin 3.