Valosin-containing protein (VCP) promotes the growth, invasion, and metastasis of colorectal cancer through activation of STAT3 signaling

Abstract

Valosin-containing protein (VCP) was previously shown to exhibit high expression in colorectal cancer (CRC) tissues as compared with that in normal tissues; however, the role of VCP in human CRC cells has remained to be elucidated. Two colorectal cancer cell lines HCT116 and RKO were used in the experiment. We introduced lentiviral constructs expressing VCP to infect RKO cells and lenti-shRNA targeting VCP into HCT116 cells, respectively. Cell proliferation, invasion, apoptosis, and cell cycle arrest were subsequently examined by MTT assay, transwell chamber assay, flow cytometry, and western blot analysis, respectively. Furthermore, a subcutaneous tumor mouse model and lung metastasis model was used to investigate the effects of VCP on the growth and metastasis of CRC cells in vivo. VCP knockdown was shown to inhibit cell proliferation, chemoresistance and invasion, and induce apoptosis in the HCT116 CRC cells, whereas VCP over-expression suppressed apoptosis and chemoresponse, promoted proliferation and invasion of the RKO CRC cells. In addition, in the subcutaneous tumor and lung metastasis mouse model, VCP knockdown in HCT116 cells suppressed carcinogenesis and metastasis in vivo. The findings of the present study indicated that VCP is very important for the proliferation and metastasis of CRC; therefore, targeting VCP and its downstream targets may represent novel therapies for the treatment of CRC.Electronic supplementary materialThe online version of this article (doi:10.1007/s11010-016-2746-6) contains supplementary material, which is available to authorized users.

Interleukin‐6 induced overexpression of valosin‐containing protein (VCP)/p97 is associated with androgen‐independent prostate cancer (AIPC) progression

“…RNAi mediated depletion of VCP induces the apoptotic cell death in Hela cells (Wojcik, Yano, & DeMartino, ). Higher expression VCP has a positive correlation with the proliferation and metastasis of colorectal cancer (Fu et al, ). In our study, downregulation or inhibition of VCP diminishes cell growth and anchorage independent growth of PCa cells.…”

“…Among the altered proteins, valosin‐containing protein (VCP) is a member of the AAA ATPases was identified as overexpressed protein which formed a central node in protein network analysis. Elevated VCP expression show positive correlation with progression, metastatic potential of Non‐small cell lung cancer (NSCLC), Ovarian, Colorectal cancer, and Osteosarcoma (Bastola, Neums, Schoenen, & Chien, ; Fu et al, ; Long, Zhang, Liu, Huang, & Luo, ; Valle et al, ). Furthermore, it has been reported that elevated VCP expression would lead to the poor prognosis of PCa (Tsujimoto et al, ).…”

“…Elevated VCP expression show positive correlation with progression, metastatic potential of Non-small cell lung cancer (NSCLC), Ovarian, Colorectal cancer, and Osteosarcoma (Bastola, Neums, Schoenen, & Chien, 2016;Fu et al, 2016;Long, Zhang, Liu, Huang, & Luo, 2013;Valle et al, 2011). Furthermore, it has been reported that elevated VCP expression would lead to the poor prognosis of PCa (Tsujimoto et al, 2004).…”

B-Cell Receptor-Associated Protein 31 Regulates the Expression of Valosin-Containing Protein Through Elf2

“…The knockdown of Bap31 arrests the cell cycle at the G0/G1 phase Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry [34]. The protein levels of cyclin D1, cyclin E, CDK2, CDK4, Ki-67 and PCNA were decreased in shRNA-VCP-transfected cells [26]. Moreover, ER stress marker levels were increased in Bap31 knockout mice after tunicamycin injection compared with those in control mice [35].…”

“…In addition, Bcl2, which is an important anti-apoptosis molecule, regulates the cell cycle by enhancing G0 and delaying the G0 to S transition. Its noted that the knockdown of VCP downregulates the protein levels of Bcl2 [26]. VCP regulates the expression levels of Bap31 maybe via the Bcl2 mediated cell cycle.…”