HACD2 Promotes Pancreatic Cancer Progression by Enhancing PKM2 Dissociation From PRKN in a Dehydratase-Independent Manner.

3-Hydroxyacyl-CoA dehydratase 2 (HACD2), an obesity-related gene involved in the elongation of long-chain fatty acids, is highly expressed in pancreatic cancer (PC) and is associated with patient prognosis. Interestingly, the study reveals that HACD2 mediated the proliferation of PC cells in a dehydratase-independent manner, affecting the downstream glycolytic pathway. Mechanistically, HACD2 promotes PC cells proliferation by binding to E3 ubiquitin-protein ligase parkin (PRKN) and enhancing pyruvate kinase PKM (PKM2) dissociation from PRKN, resulting in reduced ubiquitination of PKM2 and increased dimerization of PKM2, which subsequently promote c-Myc expression and tumor growth.

ROCK1 regulates glycolysis in pancreatic cancer via the c-MYC/PFKFB3 pathway.

Background: Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is involved in the metastasis and progression of various malignant tumors. However, how one of the isomers, ROCK1, regulates glycolysis in tumor cells is incompletely understood. Here, we attempted to elucidate how ROCK1 influences pancreatic cancer (PC) progression by regulating glycolytic activity.