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Updated: May 1, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

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FDFT1 Acts as a Negative Regulator of Autophagy by Modulating AMPK-ULK1 Signaling in Hepatocellular Carcinoma Cells

Thi Ha Nguyen1, Yongook Lee1, Minh Tuan Nguyen1

  • 1College of Pharmacy, Dongguk University, Seoul 10326, Republic of Korea.

Biomolecules & Therapeutics
|April 30, 2026
PubMed

Insights

Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) negatively regulates autophagy in liver cancer. Loss of FDFT1 increases autophagy, impacting cellular homeostasis and tumor growth, suggesting FDFT1 as a therapeutic target.

Area of Science:

  • Cellular Biology
  • Cancer Research
  • Metabolism

Background:

  • Autophagy maintains cellular homeostasis but its role in cancer is context-dependent.
  • Farnesyl-diphosphate farnesyltransferase 1 (FDFT1), an enzyme in the mevalonate pathway, has poorly understood functions in hepatocellular carcinoma (HCC) and autophagy.
  • Understanding FDFT1's role is crucial for liver cancer research.

Purpose of the Study:

  • To investigate the function of FDFT1 in regulating autophagy in HCC cells.
  • To elucidate the molecular mechanisms by which FDFT1 affects autophagy.
  • To explore FDFT1 as a potential therapeutic target and prognostic marker in liver cancer.

Main Methods:

  • Investigated FDFT1's effect on autophagy in HCC cells through loss-of-function and overexpression studies.
  • Assessed autophagosome formation and lysosomal fusion.
  • Analyzed the involvement of AMPK-ULK1 signaling pathway.

Main Results:

  • FDFT1 was identified as a negative regulator of autophagy in HCC cells.
  • Loss of FDFT1 expression resulted in increased autophagosome formation and lysosomal fusion.
  • Overexpression of FDFT1 suppressed both basal and induced autophagy.
  • Changes in autophagy correlated with AMPK-ULK1 signaling.

Conclusions:

  • FDFT1 connects cholesterol metabolism to autophagy regulation in liver cancer.
  • FDFT1 influences a central pathway controlling autophagy via AMPK-ULK1 signaling.
  • FDFT1 represents a potential prognostic marker and therapeutic target for HCC.
Keywords:
AMPK/ULK1AutophagyCholesterolFDFT1Liver cancer

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