Related Experiment Video

Updated: Apr 12, 2026

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

20.1K

Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity

Zhen Sun1, Bernard Linares1, Cassidy Urdiales1

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Science Advances
|April 10, 2026
PubMed

Insights

Activating AMP-activated protein kinase (AMPK) significantly reduced liver cancer (hepatocellular carcinoma) development in mouse models. This therapeutic strategy targets metabolic disorders linked to cancer, offering new insights into treatment possibilities.

Area of Science:

  • Hepatocellular Carcinoma (HCC) Research
  • Metabolic Regulation
  • Cancer Biology

Background:

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, often linked to metabolic disorders like obesity and type 2 diabetes.
  • AMP-activated protein kinase (AMPK), a key metabolic regulator, is downregulated in HCC, but its precise role in cancer development remains unclear.

Purpose of the Study:

  • To investigate the potential of constitutive AMP-activated protein kinase (AMPK) activation in preventing hepatocellular carcinoma (HCC) development.
  • To elucidate the mechanisms by which AMPK activation impacts HCC progression.

Main Methods:

  • Utilized a constitutively active AMPK transgenic mouse model.
  • Employed a pharmacological AMPK activator in diethylnitrosamine (DEN)-induced and streptozotocin-induced (STAM) HCC mouse models.

Main Results:

  • AMPK activation substantially reduced tumor formation in both DEN- and STAM-induced HCC models.
  • AMPK activation altered bile acid metabolism and inhibited hepatic nuclear factor alpha (HNF4α) signaling pathways.

Conclusions:

  • Constitutive AMPK activation demonstrates a preventative effect against hepatocellular carcinoma (HCC) development.
  • AMPK activation's anti-tumorigenic effects are mediated through modulation of bile acid metabolism and HNF4α signaling.
  • AMPK represents a potential therapeutic target for HCC, underscoring the link between metabolic dysfunction and cancer.

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.7K
In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

1.1K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.4K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
9.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
8.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
14.1K