The INPP4B Tumor Suppressor Modulates EGFR Trafficking and Promotes Triple-Negative Breast Cancer.

ABSTRACT: Inactivation of the tumor suppressor lipid phosphatase INPP4B is common in triple-negative breast cancer (TNBC). We generated a genetically engineered TNBC mouse model deficient in INPP4B. We found a dose-dependent increase in tumor incidence in INPP4B homozygous and heterozygous knockout mice compared with wild-type (WT), supporting a role for INPP4B as a tumor suppressor in TNBC. Tumors derived from INPP4B knockout mice are enriched for AKT and MEK gene signatures. Consequently, mice with INPP4B deficiency are more sensitive to PI3K or MEK inhibitors compared with WT mice. Mechanistically, we found that INPP4B deficiency increases PI(3,4)P₂ levels in endocytic vesicles but not at the plasma membrane. Moreover, INPP4B loss delays

SUBMITTER: Liu H 

PROVIDER: S-EPMC7415683 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature