PTEN Oxidation Promotes Constitutive PI3K Signaling and Inducible Macropinocytosis in Pancreatic Cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is defined by the near universal occurrence of KRAS mutations. The KRASG12R mutation is detected in approximately 15% to 20% of patients with PDAC and rare in other KRAS-mutant cancers. KRASG12R is unable to activate the lipid kinase PIK3CA, suggesting that alternative mechanisms might be employed to activate KRASG12R-independent PI3K signaling in PDAC. In this study, we detected elevated expression of all four PI3K isoforms in PDAC cell lines, with the PIK3CG isoform showing higher overall expression in KRASG12R-mutant PDAC. All four PI3K isoforms contributed to global PI3K signaling, and inhibition of any single isoform was insufficient to limit PDAC proliferation. The combined inhibition of all PI3K isoforms was required to limit proliferation, pr

SUBMITTER: Burge RA 

PROVIDER: S-EPMC12614194 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature