Fig. 7.
PCK1 expression is reduced in HCC tissues and is positively correlated with pAMPK and p27Kip1 expression. a, b Correlation between CDKN1B, CCNE1, and PCK1. Correlation between mRNA expression levels of a CDKN1B or b CCNE1 and PCK1 based on data from 371 HCC patients from the TCGA database mRNA dataset. Statistical analysis was performed using Pearson’s correlation coefficient (P < 0.0001). c PCK1, pAMPK, and p27Kip1 protein levels in 20 paired primary HCC tissues and adjacent non-tumor tissues. β-actin was used as a loading control. d Representative IHC images of PCK1 and pAMPK in HCC and adjacent non-tumor tissues. Magnification, 200×. e Proposed model for activation of AMPK and cell cycle arrest in PCK1-induced inhibition of hepatoma cell growth. The gluconeogenic enzyme PCK1 catalyzes an energy-consuming reaction, which consumes GTP to generate GDP. PCK1 induces AMPK activation via ATP-dependent mechanisms both in hepatoma cells and in vivo. AMPK activation further promotes G1/S transition by regulating p27Kip1 expression and negatively modulating pCDK2, cyclin E1, and pRB expression. Eventually, PCK1 inhibits the growth of hepatoma cells and the development of HCC through AMPK activation and cell cycle arrest