INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer.
Samuel J Rodgers, Lisa M Ooms, Viola MJ Oorschot, Ralf B Schittenhelm, Elizabeth V Nguyen, Sabryn A Hamila, Natalie Rynkiewicz, Rajendra Gurung, Matthew J Eramo, Absorn Sriratana, Clare G Fedele, Franco Caramia, Sherene Loi, Genevieve Kerr, Helen E Abud, Georg Ramm, Antonella Papa, Andrew M Ellisdon, Roger J Daly, Catriona A McLean Show all
Nature Communications | Published : 2021
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 ..View full abstract