INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer.

ABSTRACT: INPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P₂ to PI(3)P and INPP4B inactivation is common in triple-negative breast cancer. Paradoxically, INPP4B is also a reported oncogene in other cancers. How these opposing INPP4B roles relate to PI3K regulation is unclear. We report PIK3CA-mutant ER⁺ breast cancers exhibit increased INPP4B mRNA and protein expression and INPP4B increased the proliferation and tumor growth of PIK3CA-mutant ER⁺ breast cancer cells, despite suppression of AKT signaling. We used integrated proteomics, transcriptomics and imaging to demonstrate INPP4B localized to late endosomes via interaction with Rab7, which increased endosomal PI3Kα-dependent PI(3,4)P₂ to PI(3)P conversion, late endosome/lysosome number and car

SUBMITTER: Rodgers SJ 

PROVIDER: S-EPMC8149851 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature