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

FEBS Letters

article

Bruno Pereira De Carvalho¹  Yi-Jye Chern¹  Jiabei He¹  Chia-Hsin Chan¹ 

[1] Department of Pharmacological Sciences, Stony Brook University;Stony Brook Cancer Center, Stony Brook University

关键词: CDC42;    cell migration;    cytoskeleton rearrangements;    filopodia;    focal adhesion;    RHOA;    RNF8;    triple-negative breast cancer;   

DOI  :  10.1002/1873-3468.13999

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown