Kindlin-2 inhibited the growth and migration of colorectal cancer cells
Kindlin-2 inhibited the growth and migration of colorectal cancer cells
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DOI：
10.1007/s13277-015-3044-8
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发表时间：
2015-06-01
期刊：
影响因子：
--
通讯作者：
Huang, He
中科院分区：
文献类型：
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作者：
Ren, Yuanyuan;Jin, Hongsong;Huang, He
无翼蛋白(Wnt)/ β -连环蛋白信号的激活是结直肠癌（CRC）的一个标志。研究Wnt/ β -连环蛋白信号超激活的分子机制，寻找新的治疗靶点具有重要意义。整合素调控因子Kindlin-2最近被发现参与肿瘤的发生。然而，其表达谱和在结直肠癌进展中的功能仍然知之甚少。我们发现Kindlin-2在结直肠癌组织中表达下调。此外，在CRC细胞和正常结肠上皮细胞中，Kindlin-2过表达抑制了细胞的增殖和迁移，而Kindlin-2的下调在体外和体内均促进了CRC细胞的成瘤性。机制上，Kindlin-2降低糖原合成酶激酶（GSK） 3 β中Ser9的磷酸化，促进β -连环蛋白的泛素化。综上所述，我们的研究表明Kindlin-2在结直肠癌发病机制中的抑制作用。
Activation of Wingless (Wnt)/beta-catenin signaling is a hallmark of colorectal carcinoma (CRC). It is very important to find out the molecular mechanism for the hyperactivation of Wnt/beta-catenin signaling and identify novel therapeutic targets. Kindlin-2, a regulator of integrins, recently has been found to be involved in the tumorigenesis. However, its expression profile and functions in the progression of CRC remain poorly understood. Here, we found that the expression of Kindlin-2 was downregulated in the CRC tissues. Moreover, overexpression of Kindlin-2 in CRC cells and normal colon epithelial cells inhibited cell proliferation and migration, while downregulation of Kindlin-2 promoted the tumorigenecity of CRC cells in vitro and in vivo. Mechanistically, Kindlin-2 decreased the phosphorylation of Ser9 in glycogen synthase kinase (GSK) 3beta and promoted the ubiquitination of beta-catenin. Taken together, our study suggests the suppressive roles of Kindlin-2 in the pathogenesis of CRC.