Fig. 8: A model for how PIK3CA helical domain mutations promote oncogenesis.
From: Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer
PIK3CA helical domain mutations promote oncogenesis through two independent pathways: (1) p110α helical domain mutant protein directly interacts with IRS1 to activate the canonical PDK1-AKT pathway12; and (2) p85β translocates into the nucleus, stabilizes EZH1/2 by recruiting deubiquitinase USP7, and enhances H3K27 trimethylation. Simultaneously targeting both pathways with Alpelisib, a p110α inhibitor, and Tazemetostat, an EZH2 inhibitor, induces regression of tumors harboring a PIK3CA helical domain mutation.
