title: Rac1 is correlated with aggressiveness and a potential therapeutic target for gastric cancer.
abstract: Rac1 is a member of the Rho GTPase family. Rac1 activity is critical in regulating cytoskeleton organization and thus, modulates a diverse spectrum of cellular functions in normal and malignant cells. The aims of the present study were to investigate the expression pattern and clinical significance of Rac1, as well as the role of Rac1 in gastric cancer tumorigenesis and metastasis. The expression of Rac1 in human gastric cancer was explored by immunohistochemistry. The correlation of Rac1 expression with the clinicopathological characteristics and the survival of patients were analyzed by Pearson's Chi-square and Kaplan-Meier analyses, respectively. Rac1 overexpression cell model was used to examine in vitro and in vivo effects of Rac1 in cell growth, migration and invasion. Rac1 was highly expressed in gastric cancer tissues and correlated with differentiation, local invasion, lymph node metastasis and Lauren's classification. Rac1 expression in gastric cancer predicted shorter survival. Overexpression of Rac1 in gastric cancer cells dramatically induced Rac1 activation and rendered a more aggressive phenotype such as increased cell growth and migration/invasion in vitro and in vivo. Inhibiting Rac1 activity by specific inhibitor abrogated the effects of Rac1 on the malignant phenotype. Our clinical findings demonstrated that Rac1 was well correlated with aggressiveness and a negative prognostic factor. In addition, our data on experimental cell models supported the fundamental role of Rac1 in gastric cancer. Given its pivotal role in gastric tumorigenesis and progression, Rac1 can serve as a promising therapeutic target for gastric cancer.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Clinical Laboratory, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Clinical Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein