6-aminonicotinamide, a G6PD inhibitor, mitigates CAPS1 reduction mediated HCC metastasis via ERK and GSK3β signals.

ABSTRACT: Redirecting glucose into the pentose phosphate pathway (PPP) is a strategy used by cancer cells to facilitate accelerated proliferation and dissemination. Glucose-6-phosphate dehydrogenase (G6PD) is a rate-limiting enzyme of PPP. However, the regulation of G6PD in hepatocellular carcinoma (HCC) has not been well understood. Here we found that G6PD activity was induced in HCC tissues. G6PD inhibition, by its inhibitor 6-aminonicotinamide (6-AN) or siRNA, attenuated HCC metastasis. CAPS1 (calcium-dependent activator protein for secretion 1) was identified as a novel regulator of G6PD. CAPS1 C2 domain directly interacted with the N-terminus of G6PD. This interaction disrupted G6PD dimer formation and inhibited G6PD activity. In HCC, CAPS1 down-regulation, primarily due to miR-30d-5p elevation

SUBMITTER: Lin X 

PROVIDER: S-EPMC12547465 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature