PPP1R3C functions as a tumor suppressor in endometrial cancer through promotion of glycogen synthesis

In this study, we report a novel function of protein phosphatase 1 regulatory subunit 3C (PPP1R3C)-which is known to promote glycogenesis by activating glycogen synthase and to inhibit glycogen breakdown by suppressing glycogen phosphorylase- as a tumor suppressor in endometrial cancer. First, the expression of PPP1R3C was strongly down-regulated in uterine corpus endometrial cancer (UCEC) tissues, and ectopic expression of PPP1R3C led to cell cycle arrest and apoptosis in HEC1A and HEC1B cells derived from UCEC. PPP1R3C also inhibited the growth of xenograft tumors in BALB/c nude mice. We found evidence indicating that the activation of glycogen synthesis was at least partly responsible for the tumor suppressor activity of PPP1R3C. Specifically, inhibition of glycogen synthase abrogated the effect of ectopic PPP1R3C expression on the growth inhibition of UCEC cells. Collectively, our data indicate that PPP1R3C is a tumor suppressor gene functioning through the induction of glycogen synthesis.