PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42525774.
- Also identified by DOI 10.1126/sciadv.aed8038 and PMC identifier 13418929.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
SWI/SNF chromatin remodelers are represented by three biochemically distinct subcomplexes, the abundant cBAF and the less abundant PBAF and GBAF. Genetics have identified important roles for PBAF in development and disease; however, relating PBAF-mediated phenotypes to biochemical function in chromatin regulation and gene activation has been challenging. Here, we show that the PBRM1 subunit of PBAF is critical for the completion of TGFβ1-mediated epithelial-mesenchymal transition (EMT) of mammary cells in vitro as well as the metastasis of murine breast cancers in vivo. Using epigenomics to profile different stages of EMT, we find that PBRM1 is necessary for targeting PBAF to inducible promoters marked by H3K14ac. We further find that PBRM1 facilitates DNA accessibility at sites bound by TGFβ1-inducible transcription factors, such as Atf3, for the induction of genes involved in migration, cell survival, and inflammation, providing evidence that PBAF is a vulnerability in late-stage metastatic cancers.
Medical subject headings
- Epithelial-Mesenchymal Transition
- Breast Neoplasms
- Transcription Factors
- DNA-Binding Proteins
- Nuclear Proteins