High expression levels of PUMA are correlated with decreased mitochondrial pyruvate uptake and increased glycolysis in HCCs and poor prognosis of HCC patients.
PUMA is a pro-apoptotic Bcl-2 family protein that can act as a tumor suppressor or oncogene in different cancers.In this issue, Kim et al. show that PUMA, independent of its apoptotic function, enforces glycolytic metabolism by inhibiting the transport of pyruvate into the mitochondria, promoting hepatocellular carcinoma.
Here, we show that inclusion of microRNA target sites in therapeutic mRNAs encoding apoptotic proteins, Caspase or PUMA, can prevent their expression in healthy hepatocytes while triggering apoptosis in hepatocellular carcinoma cells.
The increased expression of PUMA in malignant hepatocellular cells relative to that in non-tumor hepatocytes suggests that PUMA expression may play a role in HCC development.
The increased expression of PUMA in malignant hepatocellular cells relative to that in non-tumor hepatocytes suggests that PUMA expression may play a role in HCC development.
We used a recombinant adenovirus that carries a lethal gene [p53-up-regulated modulator of apoptosis (PUMA)] under the control of a beta-catenin/Tcf-responsive promoter (AdTOP-PUMA) to selectively target human colorectal cancer cells (SW480, HCT116, DLD-1, and LS174T), hepatocellular carcinoma (HepG2), and gastric cancer cells (AGS) in which the beta-catenin/Tcf pathway is activated, and compared its efficiency in killing cancer cells in which this pathway is inactive or only weakly active.