title: RhoC protein stimulates migration of gastric cancer cells through interaction with scaffold protein IQGAP1.
abstract: The scaffold protein IQGAP1 is closely related to certain Rho GTPases. Research has revealed that IQGAP1 acts as an effector of Cdc42 and Rac1 in the regulation of cell activity such as proliferation and migration. However, whether IQGAP1 is associated with RhoC, another important Rho GTPase, is unclear. Previous results from our laboratory indicated that IQGAP1 and RhoC are highly expressed in gastric cancer tissues and cells. This study was designed to investigate the possible interaction between IQGAP1 and RhoC in the regulation of the migration of cancer cells. The expression of IQGAP1 and RhoC in gastric cancer tissues and cell lines was detected by Western blotting. siRNAs targeting IQGAP1 or RhoC were transfected into gastric cancer cells to knock down the expression of the proteins. Adenoviral constructs encoding full length IQGAP1, the C‑terminal fragment of IQGAP1, and the constitutively active RhoC gene were used to infect gastric cancer cells to increase the expression of the proteins. The migratory activity of a gastric cancer cell line was measured by a transwell migration assay. Western blotting revealed that the IQGAP1 and RhoC proteins were highly expressed in gastric cancer tissues and cells. Spearman's rank correlation analysis indicated that the increases in the expression of IQGAP1 and RhoC were closely correlated. The transwell migration assay revealed that both IQGAP1 and RhoC stimulated the migration activity of the gastric cancer cell line AGS. The knockdown of IQGAP1 expression by siRNA blocked the migration‑stimulating activity of RhoC, while the knockdown of RhoC expression had no effect on the migration-stimulatory activity of IQGAP1. Co-IP results showed that RhoC and IQGAP1 bound to each other. These results reveal a previously unrecognized interaction between IQGAP1 and RhoC, and demonstrate that IQGAP1 is a downstream effector of RhoC in the regulation of the migration activity of gastric cancer cells.
authors.affiliation: Jiangsu University, Zhenjiang, Jiangsu 212013, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Yong-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Sang
authors.forename: Wen-Rong
authors.initials: WR
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D020703:ras GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D034741:RNA, Small Interfering; D020703:ras GTPase-Activating Proteins; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein