title: 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.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China.
authors.forename: Qianfeng
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Clinical Laborotary, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China.
authors.forename: Daxin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China. fuqianfeng2016@yeah.net.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse
keywords: Colorectal cancer; Metastasis; Proliferation; STAT3; Valosin-containing protein