FDFT1 Acts as a Negative Regulator of Autophagy by Modulating AMPK–ULK1 Signaling in Hepatocellular Carcinoma Cells
10.4062/biomolther.2025.178
- Author:
Thi Ha NGUYEN
1
;
Yongook LEE
;
Minh Tuan NGUYEN
;
Seoung Gyu CHOI
;
Phuong Ngan NGUYEN
;
Boram KIM
;
Eun Ji KIM
;
Gyeoung Jin KANG
;
Mi Kyung PARK
;
Sung Hoon LEE
;
Sang Geon KIM
;
Chang Hoon LEE
Author Information
1. College of Pharmacy, Dongguk University, Seoul 10326, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2026;34(3):632-640
- CountryRepublic of Korea
- Language:English
-
Abstract:
Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.
