Related Experiment Video

Updated: Jun 3, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
06:38

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

Published on: September 12, 2019

The role of JNK in the development of hepatocellular carcinoma

Madhumita Das1, David S Garlick, Dale L Greiner

  • 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

Genes & Development
|March 17, 2011
PubMed

Insights

The cJun NH(2)-terminal kinase (JNK) pathway has a dual role in liver cancer. While promoting inflammation that supports tumor growth, JNK in liver cells actually reduces tumor development.

Area of Science:

  • Oncology
  • Signal Transduction
  • Hepatology

Background:

  • The cJun NH(2)-terminal kinase (JNK) pathway is implicated in hepatocellular carcinoma growth.
  • The precise role of JNK in regulating tumor progression remains unclear.

Purpose of the Study:

  • To elucidate the dual role of JNK signaling in hepatocellular carcinoma development.
  • To investigate the impact of JNK isoforms (JNK1 and JNK2) deficiency in hepatocytes and nonparenchymal cells on liver cancer.

Main Methods:

  • Utilized compound deficiency models for JNK1 and JNK2 in hepatocytes and nonparenchymal cells.
  • Assessed hepatocellular carcinoma development, tumor burden, and hepatic inflammation.

Main Results:

  • Compound JNK deficiency in hepatocytes did not prevent hepatocellular carcinoma but increased tumor burden.
  • JNK deficiency in both hepatocytes and nonparenchymal cells reduced hepatic inflammation and tumorigenesis.
  • JNK signaling exhibits context-dependent effects in liver cancer progression.

Conclusions:

  • JNK plays a dual role in hepatocellular carcinoma: promoting an inflammatory environment conducive to tumor growth while simultaneously suppressing tumor development within hepatocytes.
  • Targeting JNK signaling may offer therapeutic strategies for liver cancer, but requires careful consideration of cell-specific effects.

More Related Videos

Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice10:35

Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice

Published on: September 25, 2013

Related Concept Videos

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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
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...
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...