KMT5A-methylated SNIP1 promotes triple-negative breast cancer metastasis by activating YAP signaling.

ABSTRACT: Smad nuclear-interacting protein 1 (SNIP1) is a transcription repressor related to the TGF-β signaling pathway and associates with c-MYC, a key regulator of cell proliferation and tumor development. Currently, the mechanism by which SNIP1 regulates tumorigenesis and cancer metastasis is unknown. Here, we identify that SNIP1 is a non-histone substrate of lysine methyltransferase KMT5A, which undergoes KMT5A-mediated mono-methylation to promote breast cancer cell growth, invasion and lung metastasis. Mechanistically, we show KMT5A-mediated K301 methylation of SNIP1 represents a sensing signal to release histone acetyltransferase KAT2A and promotes the interaction of c-MYC and KAT2A, and the recruitment of c-MYC/KAT2A complex to promoter of c-MYC targets. This event ultimately inhibits the Hi

SUBMITTER: Yu B 

PROVIDER: S-EPMC9023492 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature