title: Loss of ARHGDIA expression is associated with poor prognosis in HCC and promotes invasion and metastasis of HCC cells.
abstract: Rho GTPases control a wide range of cellular processes and contribute to tumor invasion and metastasis. As a regulator of Rho activity, ARHGDIA is aberrantly expressed in several types of tumors and plays different roles in the tumor process. To elucidate the role of ARHGDIA in HCC, we investigated the patterns of its expression, prognosis and clinical profiles in HCC. Functional assays were performed to investigate whether the alteration of ARHGDIA has an effect on cell growth, migration and invasion, as well as the status of Rho GTPases. We found that ARHGDIA was frequently downregulated in HCC and associated with tumor invasion and metastasis. Moreover, ARHGDIA was significantly associated with OS and TTR of HCC patients. Low level of ARHGDIA exhibited a decreased postoperative OS and a shorter TTR compared those with high levels. Functional assays showed that loss of ARHGDIA promoted HCC cell migration and invasion in vitro and lung metastasis formation in vivo. We found that loss of ARHGDIA significantly induced Rac1 and RhoA activation which may contribute to invasion and metastasis of HCC. In conclusion, the present study has identified loss of ARHGDIA contributed to the processes of hepatic tumorigenesis, in particular invasion and metastasis which may provide a potential therapeutic target for HCC.
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Li Yong
authors.initials: LY
authors.lastname: Huang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Da Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Yu Wei
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Xin Xiang
authors.initials: XX
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: San Jun
authors.initials: SJ
authors.lastname: Cai
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis; D011379:Prognosis; D014161:Transduction, Genetic; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000032:analysis / Q000096:biosynthesis*
chemical_list: C569638:ARHGDIA protein, human; D014408:Biomarkers, Tumor; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha