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R ho J modulates melanoma invasion by altering actin cytoskeletal dynamics
Author(s) -
Ho Hsiang,
Soto Hopkin Amelia,
Kapadia Rubina,
Vasudeva Priya,
Schilling Jonathan,
Ganesan Anand K.
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12058
Subject(s) - cytoskeleton , cofilin , melanoma , microbiology and biotechnology , actin , biology , cell migration , in vitro , actin cytoskeleton , cancer research , chemistry , cell , biochemistry
Summary R ho family GTP ases 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 CDC 42 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 ( ARP 2/3 complex subunit) in a PAK 1‐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 PAK 1.