Integrative Proteogenomics and Forward Genetics Reveal a Novel Mitotic Vulnerability in Triple-Negative Breast Cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with few effective targeted therapies. Taxanes and other microtubule-targeting agents (MTA) are first-line chemotherapies for TNBC; however, the molecular mechanisms that underlie TNBC taxane sensitivity are largely unknown, preventing selection of taxane-responsive patients and development of more selective therapeutic strategies. In this study, we identified tumor-selective vulnerabilities in TNBC harboring inactivation of the tumor suppressor PTPN12 by integrating proteogenomic characterization and synthetic lethality screening. We discovered that PTPN12 inactivation drives mitotic defects through aberrant hyperactivation of the ubiquitin ligase complex APCFZR1, a critical regulator of the cell cycle. Consist

SUBMITTER: Neill NJ 

PROVIDER: S-EPMC12641601 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature