title: RhoJ modulates melanoma invasion by altering actin cytoskeletal dynamics.
abstract: Rho family GTPases regulate diverse processes in human melanoma ranging from tumor formation to metastasis and chemoresistance. In this study, a combination of in vitro and in vivo approaches was utilized to determine whether RHOJ, a CDC42 homologue that regulates melanoma chemoresistance, also controls melanoma migration. Depletion or overexpression of RHOJ altered cellular morphology, implicating a role for RHOJ in modulating actin cytoskeletal dynamics. RHOJ depletion inhibited melanoma cell migration and invasion in vitro and melanoma tumor growth and lymphatic spread in mice. Molecular studies revealed that RHOJ alters actin cytoskeletal dynamics by inducing the phosphorylation of LIMK, cofilin, and p41-ARC (ARP2/3 complex subunit) in a PAK1-dependent manner in vitro and in tumor xenografts. Taken together, these observations identify RHOJ as a melanoma linchpin determinant that regulates both actin cytoskeletal dynamics and chemoresistance by activating PAK1.
authors.affiliation: Department of Medicine, University of California, Irvine, Irvine, CA, USA.
authors.forename: Hsiang
authors.initials: H
authors.lastname: Ho
authors.forename: Amelia
authors.initials: A
authors.lastname: Soto Hopkin
authors.forename: Rubina
authors.initials: R
authors.lastname: Kapadia
authors.forename: Priya
authors.initials: P
authors.lastname: Vasudeva
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schilling
authors.forename: Anand K
authors.initials: AK
authors.lastname: Ganesan
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays; D054462:p21-Activated Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D054462:p21-Activated Kinases; C417188:RHOJ protein, human; D020741:rho GTP-Binding Proteins