Abstract
Cdc37 is an important partner for HSP90, assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases. Given its influence on cell growth pathways, Cdc37 has been discussed as a potential intermediate in carcinogenesis. However, to date, the potential functional roles and molecular mechanisms by which Cdc37 regulated cell survival remained unclear in colorectal carcinoma. Here, we investigated the expression of Cdc37 and its clinical significance in colorectal carcinoma, and systematically explored the role of Cdc37 in colorectal carcinoma cell survival both in vitro and in vivo and the underlying mechanism. Our results showed that Cdc37 was remarkably up-regulated in colorectal carcinoma, which facilitated cell survival mainly by promoting cell proliferation, G1-S transition, and inhibiting cell apoptosis. Our data further indicated that Cdc37 increased the stability of CDK4 to activate the RB1 signaling pathway, followed by the increased expression of Bcl-2 and Bcl-xL, which ultimately promoted the cell survival in colorectal carcinoma. Moreover, knockdown of CDK4 reversed the Cdc37-mediated effect in promoting the progression of CRC. Our findings demonstrated that Cdc37 played a critical role in promoting colorectal carcinoma cell survival by increasing CDK4 stability to activate the RB1 signaling pathway. Thereby, Cdc37 might serve as a potential therapeutic target in CRC patient.
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