Glycogen synthase kinase-3β inhibition promotes lysosome-dependent degradation of c-FLIP_L in hepatocellular carcinoma.

ABSTRACT: Glycogen synthase kinase-3β (GSK-3β) is a ubiquitously expressed serine/threonine kinase involved in a variety of functions ranging from the control of glycogen metabolism to transcriptional regulation. We recently demonstrated that GSK-3β inhibition triggered ASK1-JNK-dependent apoptosis in human hepatocellular carcinoma (HCC) cells. However, the comprehensive picture of downstream GSK-3β-regulated pathways/functions remains elusive. In this study, we showed that GSK-3β was aberrantly activated in HCC. Pharmacological inhibition and genetic depletion of GSK-3β suppressed the growth and induced caspase-dependent apoptosis in HCC cells. In addition, GSK-3β inhibition-induced apoptosis through downregulation of c-FLIP_L in HCC, which was caused by biogenesis of functional lysosomes

SUBMITTER: Zhang N 

PROVIDER: S-EPMC5833564 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature