Cdc37 facilitates cell survival of colorectal carcinoma via activating the CDK4 signaling pathway. Issue 3 (16th February 2018)

• Record Type: Journal Article
• Authors: Zhu, Jianjun; Yan, Fang; Tao, Jia; Zhu, Xiaohua; Liu, Jiayou; Deng, Shishan; Zhang, Xiaoming
• Is Part Of: Cancer science. Volume 109:Issue 3(2018)
• Page Start: 656
• Page End: 665
• Publication Date: 2018-02-16
• Subjects: Cdc37 -- CDK4 -- cell survival -- colorectal carcinoma -- p‐RB1; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13495
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Cell division cycle 37 (Cdc37) is an important partner for heat shock protein 90 (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 regulates cell survival in colorectal carcinoma (CRC) remain unclear. Here, we investigated the expression of Cdc37 and its clinical significance in CRC, and systematically explored the role and the underlying mechanism of Cdc37 in CRC cell survival both in vitro and in vivo. Our results showed that Cdc37 was remarkably up‐regulated in CRC, 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 cyclin‐dependent kinase 4 (CDK4) to activate the retinoblastoma 1 (RB1) signaling pathway, followed by increased expression of Bcl‐2 and Bcl‐xL, which ultimately promoted cell survival in CRC. Moreover, knockdown of CDK4 reversed the Cdc37‐mediated effect in promoting the progression of CRC. Our findings showed that Cdc37 played a critical role in promoting CRC cell survival by increasing CDK4 stability to activate the RB1 signaling pathway. Thereby, Cdc37 might serve as a potential therapeutic target in CRC patients. Abstract : Cdc37 is up‐regulated in CRC; Up‐regulated Cdc37 promotes CRC cell survival; Cdc37 promotes CRC cell survival by activating the CDK4/p‐RB1 signaling pathway.