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

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract 3‐Hydroxyacyl‐CoA dehydratase 2 (HACD2), an obesity‐related gene involved in the elongation of long‐chain fatty acids, is highly expressed pancreatic cancer (PC) and associated with patient prognosis. Interestingly, study reveals that HACD2 mediated proliferation PC cells a dehydratase‐independent manner, affecting downstream glycolytic pathway. Mechanistically, promotes by binding to E3 ubiquitin‐protein ligase parkin (PRKN) enhancing pyruvate kinase PKM (PKM2) dissociation from PRKN, resulting reduced ubiquitination PKM2 increased dimerization PKM2, which subsequently promote c‐Myc expression tumor growth. Moreover, overexpression‐induced growth mitigated knockdown or overexpression PRKN. Furthermore, weight loss drug orlistat, potentially binds HACD2, disrupted interaction between PRKN further PKM2. Therefore, this elucidates mechanism regulates through noncanonical signaling pathway, may provide potential new target strategy for individualized clinical treatment PC.

Язык: Английский

Polyphenol-based pH-responsive nanoparticles enhance chemo-immunotherapy in pancreatic cancer

Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 615 - 629

Опубликована: Фев. 16, 2025

Язык: Английский

Decoding STING’s roles in cancer: immunity, pain, dormancy, and autophagy

Molecular and Cellular Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Язык: Английский