Open AccessPerturbation of BRMS1 interactome reveals pathways that impact metastasis
Author(s) -
Rosalyn C Zimmermann,
Mihaela E. Sardiu,
Christa A. Manton,
Sayem Miah,
Charles A.S. Banks,
Mark K. Adams,
Devin C. Koestler,
Douglas R. Hurst,
Mick D. Edmonds,
Michael P. Washburn,
Danny R. Welch
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0259128
Subject(s) - interactome , metastasis , biology , cancer research , dna damage , cdkn2a , microbiology and biotechnology , bioinformatics , cancer , computational biology , gene , dna , genetics
Breast Cancer Metastasis Suppressor 1 (BRMS1) expression is associated with longer patient survival in multiple cancer types. Understanding BRMS1 functionality will provide insights into both mechanism of action and will enhance potential therapeutic development. In this study, we confirmed that the C-terminus of BRMS1 is critical for metastasis suppression and hypothesized that critical protein interactions in this region would explain its function. Phosphorylation status at S237 regulates BRMS1 protein interactions related to a variety of biological processes, phenotypes [cell cycle (e.g., CDKN2A), DNA repair (e.g., BRCA1)], and metastasis [(e.g., TCF2 and POLE2)]. Presence of S237 also directly decreased MDA-MB-231 breast carcinoma migration in vitro and metastases in vivo . The results add significantly to our understanding of how BRMS1 interactions with Sin3/HDAC complexes regulate metastasis and expand insights into BRMS1’s molecular role, as they demonstrate BRMS1 C-terminus involvement in distinct protein-protein interactions.