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The ubiquitin ligase RNF8 regulates Rho GTPases and promotes cytoskeletal changes and motility in triple‐negative breast cancer cells
Author(s) -
De Carvalho Bruno,
Chern YiJye,
He Jiabei,
Chan ChiaHsin
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13999
Subject(s) - rhoa , cdc42 , ubiquitin ligase , triple negative breast cancer , microbiology and biotechnology , cell migration , gene knockdown , gtpase , motility , rac1 , focal adhesion , cancer research , biology , chemistry , ubiquitin , cell , cancer , breast cancer , signal transduction , apoptosis , biochemistry , genetics , gene
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.