Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity
Year: 2026
Type: article
Abstract: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality and is largely driven by metabolic disorders such as obesity and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a master regulator of metabolism, and its activation has been proposed as a therapeutic strategy for treating metabolic disorders. However, although AMPK activity is down-regulated in HCC, the precise role of AMPK in HCC development has not been clearly delineated. Here, we investigated the ability of constitutive AMPK activation to prevent HCC development using a constitutively active AMPK transgenic mouse model and a pharmacological AMPK activator. We observed that AMPK activation substantially reduced tumor formation in both diethylnitrosamine (DEN)-induced and streptozocin-induced (STAM) models of HCC via altered bile acid metabolism and inhibition of hepatic nuclear factor alpha (HNF4α) signaling. These findings provide mechanistic insights into AMPK biology and highlight the potential of AMPK as a therapeutic target, emphasizing the intricate interplay between metabolic dysregulation and cancer development.
Source: Science Advances
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G1099493753, G1756901816, The functional role of mTORC1 regulation by AMPK in cellular metabolic reprogramming, G4222846132, Proteomics and Metabolomics Core Facility, Recruitment of First-Time, Tenure-Track Faculty Members, Vevo 3100 Ultrasound System, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, Decoding tumor metabolic and immunologic interactions driving different biological subtypes in patients with bladder cancer.
OpenAlex ID: W7153239692