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.

SUBMITTER: Fu Q 

PROVIDER: S-EPMC4927615 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature