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

  • 0Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China;; Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
New York +

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October 13, 2025

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October 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Cancer cells use the pentose phosphate pathway (PPP) for growth. We found calcium-dependent activator protein for secretion 1 (CAPS1) regulates glucose-6-phosphate dehydrogenase (G6PD) in liver cancer, suggesting G6PD inhibitors as a potential therapy.

Area Of Science

  • Biochemistry
  • Oncology
  • Molecular Biology

Background

  • Pentose phosphate pathway (PPP) is crucial for cancer cell proliferation.
  • Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme in the PPP.
  • G6PD regulation in hepatocellular carcinoma (HCC) remains poorly understood.

Purpose Of The Study

  • Investigate G6PD regulation in HCC.
  • Identify novel regulators of G6PD in HCC.
  • Evaluate G6PD inhibition as a therapeutic strategy for HCC.

Main Methods

  • Analysis of G6PD activity in HCC tissues.
  • Inhibition of G6PD using 6-aminonicotinamide (6-AN) and siRNA.
  • Identification and characterization of CAPS1 as a G6PD regulator.
  • Assessment of reactive oxygen species (ROS) levels and epithelial-mesenchymal transition (EMT) markers.
  • In vitro and in vivo validation of therapeutic strategies.

Main Results

  • G6PD activity is elevated in HCC tissues.
  • CAPS1 directly interacts with G6PD, inhibiting its activity.
  • Down-regulation of CAPS1, due to miR-30d-5p, promotes HCC metastasis via ROS and EMT.
  • G6PD inhibition by 6-AN or siRNA reverses HCC metastasis.
  • Therapeutic effects are observed in vitro and in vivo.

Conclusions

  • CAPS1 is a novel regulator of G6PD in HCC.
  • G6PD inhibition is a promising therapeutic strategy for HCC, particularly in patients with low CAPS1 expression.
  • Targeting G6PD offers a potential avenue for HCC treatment.

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