Secernin-2 Stabilizes Histone Methyltransferase KMT2C to Suppress Progression and Confer Therapeutic Sensitivity to PARP Inhibition in Triple-Negative Breast Cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is a difficulty and bottleneck in the clinical treatment of breast cancer due to a lack of effective therapeutic targets. Herein, we first report that secernin 2 (SCRN2), an uncharacterized gene in human cancer, acts as a novel tumor suppressor in TNBC to inhibit cancer progression and enhance therapeutic sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition both in vitro and in vivo. SCRN2 is downregulated in TNBC through chaperone-mediated autophagic degradation, and its downregulation is associated with poor patient prognosis. Moreover, SCRN2 impedes the proteasomal degradation of histone-lysine N-methyltransferase 2C (KMT2C) by recruiting Bcl2-associated athanogene 2 to block the interaction of KMT2C with E3 ubiquitin-protein ligase CHIP. Con

SUBMITTER: Huang MY 

PROVIDER: S-EPMC11905051 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature