The ubiquitin ligase RNF8 regulates Rho GTPases and promotes cytoskeletal changes and motility in triple-negative breast cancer cells

被引：5
|
作者：
Pereira De Carvalho, Bruno [1 ]
Chern, Yi-Jye [1 ]
He, Jiabei [1 ]
Chan, Chia-Hsin [1 ,2 ]
机构：
[1] SUNY Stony Brook, Dept Pharmacol Sci, Basic Sci Tower 8-121, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA
来源：
FEBS LETTERS | 2021年 / 595卷 / 02期
关键词：
CDC42; cell migration; cytoskeleton rearrangements; filopodia; focal adhesion; RHOA; RNF8; triple‐ negative breast cancer; DEGRADATION; UBIQUITYLATION; FILOPODIA; SUBSTRATE; GROWTH; CDC42;
D O I：
10.1002/1873-3468.13999
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The ubiquitin ligase RNF8 is known to induce epithelial-to-mesenchymal (EMT) transition and metastasis in triple-negative breast cancer (TNBC). Besides EMT, Rho GTPases have been shown as key regulators in metastasis. In this study, we investigated the role of RNF8 in regulating Rho GTPases and cell motility. We find that RNF8 knockdown in TNBC cells attenuates the protein and mRNA levels of Ras homolog family member A (RHOA) and cell division cycle 42 (CDC42). We show that the formation of filopodia, focal adhesions, and the association of focal adhesions to stress fibers is impaired upon RNF8 knockdown. Cell migration is significantly inhibited by RNF8 knockdown. Our study suggests a potential novel role for RNF8 in mediating cell migration in TNBC through regulation of the Rho GTPases RHOA and CDC42.
引用
收藏
页码：241 / 252
页数：12
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