Autophagy suppression via SRC induction represents a therapeutic vulnerability for <i>BAP1</i>-mutant cancers.

ABSTRACT: BAP1 is a tumor suppressor and epigenetic modifier that is frequently mutated in cancer, leading to increased aggressiveness and metastasis, as well as poor patient survival. Unfortunately, there are currently no specific therapies for metastatic tumors harboring BAP1 mutations. In this study, we have identified a new targetable BAP1-associated autophagic vulnerability. We demonstrate that BAP1 transcriptionally regulates the proto-oncogene SRC, a non-receptor tyrosine kinase. SRC then binds to, phosphorylates, and inactivates BECN1 (Beclin 1), an essential autophagy protein. This inhibits autophagy in cells derived from various cancer types with BAP1 mutations. Treatment of these cells with SRC inhibitors (such as dasatinib, bosutinib and saracatinib) and autophagy-inducing

SUBMITTER: Vega-Rubin-de-Celis S 

PROVIDER: S-EPMC12758184 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature