PSMA redirects MAPK to PI3K-AKT signaling to promote prostate cancer progression.

Increased Prostate Specific Membrane Antigen expression promotes tumor progression in prostate epithelium by dysregulating the β1-integrin/type I insulin-like growth factor receptor axis, resulting in a shift in signaling from the less aggressive mitogen-activated protein kinase-extracellular signal-regulated kinases 1 and 2 pathway to the pro-survival protein kinase B(AKT)/phosphatidylinositol 3-kinase pathway.

PSMA redirects cell survival signaling from the MAPK to the PI3K-AKT pathways to promote the progression of prostate cancer.

Increased abundance of the prostate-specific membrane antigen (PSMA) on prostate epithelium is a hallmark of advanced metastatic prostate cancer (PCa) and correlates negatively with prognosis. However, direct evidence that PSMA functionally contributes to PCa progression remains elusive. We generated mice bearing PSMA-positive or PSMA-negative PCa by crossing PSMA-deficient mice with transgenic PCa (TRAMP) models, enabling direct assessment of PCa incidence and progression in the presence or absence of PSMA.