title: Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis.
abstract: GTP binding protein 4(GTPBP4), a member of GTP-binding protein family, was previously characterized as a tumor suppressor that regulates and requires merlin to suppress cell proliferation. However, the role of GTPBP4 in the metastasis of colorectal carcinoma (CRC) remains unelucidated. Here, we observed that GTPBP4 was detected at higher levels in CRC metastatic tissues than that in the primary tumor tissues. Notably, up-regulation of GTPBP4 was closely correlated with tumor metastasis in CRCs. Kaplan-Meier and multivariate Cox regression analysis indicated GTPBP4 as an independent prognostic factor for CRC patients (hazard ratio = 2.693, 95% confident interval: 1.193-6.083, p = 0.017). Functional studies established that knockdown of GTPBP4 impeded, whereas ectopic expression of GTPBP4 enhanced cell motility and tumor metastasis in CRC cells. Interestingly, mechanistic investigations suggested that GTPBP4 may disorganize actin cytoskeleton through repressing RhoA signaling. Taken together, our research uncovered that GTPBP4 promotes CRC metastasis by disrupting actin cytoskeleton, which is mediated by the reduced RhoA activity. Strategies targeting GTPBP4 will be promising for CRC patients with metastases.
authors.affiliation: Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People's Republic of China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yu
authors.affiliation: College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036, People's Republic of China.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Abdominal Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Abdominal Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, People's Republic of China. Electronic address: xuq_2015@sina.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C066737:RHOA protein, human; D019204:GTP-Binding Proteins; C498988:GTPBP4 protein, human; D020742:rhoA GTP-Binding Protein
keywords: Actin cytoskeleton; CRC; GTPBP4; Metastasis; RhoA activity