期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 26, 期 2, 页码 -出版社
WILEY
DOI: 10.1111/pcmr.12058
关键词
RHOJ; PAK1; melanoma; migration; invasion; cytoskeleton
资金
- NIH [1K08AR056001]
- UC Cancer Research Coordinating Committee
- American Cancer Society [121540-RSG-11-128-01-CSM]
- National Center for Research Resources (NCRR) [UL1 RR031985]
- NCI [P30CA062203, 5T32CA009054-34]
- [P41-RR01192]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据