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PMID: 23253891 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

RhoJ modulates melanoma invasion by altering actin cytoskeletal dynamics.

Pigment cell & melanoma research ·Vol. 26 ·No. 2 ·2013-03-00 ·Pages 218-25

Ho H, Soto Hopkin A, Kapadia R, Vasudeva P, Schilling J, Ganesan AK

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.

MeSH Terms
Actin Cytoskeleton/metabolism Animals Cell Line, Tumor Cell Movement Cell Proliferation Enzyme Activation Humans Melanoma/enzymology,pathology Mice Models, Biological Neoplasm Invasiveness Skin Neoplasms/enzymology,pathology Xenograft Model Antitumor Assays p21-Activated Kinases/metabolism rho GTP-Binding Proteins/metabolism
Chemicals
p21-Activated Kinases RHOJ protein, human rho GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ho Hsiang
Department of Medicine, University of California, Irvine, Irvine, CA, USA.
Soto Hopkin Amelia
Kapadia Rubina
Vasudeva Priya
Schilling Jonathan
Ganesan Anand K
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Article Info
Journal
Pigment cell & melanoma research
Abbr.
Pigment Cell Melanoma Res
ISSN
1755-148X
DOI
10.1111/pcmr.12058
Published
2013-03-00
Epub
2013-00-07
Pages
218-25
Language
English
Region
England
NLM ID
101318927
PMCID
PMC4528913
Subset
IM
Grants
NCI NIH HHS · T32 CA009054 · United States
NIAMS NIH HHS · K08 AR056001 · United States
NIAMS NIH HHS · 1K08AR056001 · United States
NCI NIH HHS · 5T32CA009054-34 · United States
NCRR NIH HHS · UL1 RR031985 · United States
NCRR NIH HHS · P41 RR001192 · United States
NCI NIH HHS · P30 CA062203 · United States
NCRR NIH HHS · P41-RR01192 · United States
NCI NIH HHS · P30CA062203 · United States
External Links
PubMed source DOI: 10.1111/pcmr.12058 PMC Full Text View journal details
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