Related Experiment Video

Updated: Jan 29, 2026

Real Time Monitoring of Intracellular Bile Acid Dynamics Using a Genetically Encoded FRET-based Bile Acid Sensor
09:21

Real Time Monitoring of Intracellular Bile Acid Dynamics Using a Genetically Encoded FRET-based Bile Acid Sensor

Published on: January 4, 2016

10.4K

FGF15 Activates Hippo Signaling to Suppress Bile Acid Metabolism and Liver Tumorigenesis

Suyuan Ji1, Qingxu Liu1, Shihao Zhang1

  • 1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China.

Developmental Cell
|February 13, 2019
PubMed

Insights

Fibroblast growth factor 15 (FGF15) activates Hippo signaling to control bile acid metabolism and prevent liver overgrowth and tumors. This pathway acts as a key sensor for bile acid levels, maintaining liver health.

Area of Science:

  • Cellular signaling pathways
  • Hepatology
  • Gastroenterology

Background:

  • The external regulators of Hippo signaling are not well understood.
  • Hippo signaling plays a crucial role in organ size control and tumor suppression.

Purpose of the Study:

  • To investigate the role of FGF15 in modulating Hippo signaling.
  • To elucidate the mechanism by which FGF15 regulates bile acid metabolism and liver homeostasis.

Main Methods:

  • Investigated FGF15 induction by FXR in response to bile acids.
  • Examined the interaction of FGF15 with FGFR4, NF2, and Raf in hepatic cells.
  • Assessed the impact of Mst1/2 activation on SHP and Cyp7a1 expression.
  • Utilized pharmacological bile acid depletion in Mst1/2-deficient models.

Main Results:

  • FGF15, induced by FXR, activates Hippo signaling via FGFR4, NF2, and Raf.
  • Activated Mst1/2 phosphorylates and stabilizes SHP, downregulating Cyp7a1 expression and bile acid synthesis.
  • Mst1/2 deficiency leads to impaired bile acid metabolism and increased bile acid production.
  • Depletion of intestinal bile abrogates Mst1/2-mutant-driven liver overgrowth and oncogenesis.

Conclusions:

  • FGF15-Hippo signaling acts as a crucial gut-liver axis sensor for bile acid availability.
  • This pathway effectively restrains liver size and suppresses tumorigenesis by regulating bile acid metabolism.
Keywords:
FGF15FGFR4HCCHippo signalingNF2SHPbile acid metabolismliver growth

More Related Videos

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport08:42

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

Published on: November 27, 2016

11.6K
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.7K

Related Concept Videos

Acid Suppressive Drugs for Peptic Ulcer Disease: Antacids01:31

Acid Suppressive Drugs for Peptic Ulcer Disease: Antacids

In the complex environment of the gastric lumen, excessive acid secretion can lead to the formation or worsening of ulcers within the delicate mucosal layer. Antacids, such as sodium bicarbonate and calcium carbonate, provide relief by neutralizing this acid, transforming it into harmless salt and water. This neutralization process raises the gastric pH from a highly acidic level of 1 to a more basic 3-4, reducing the acidity within the stomach.
However, this neutralization reaction between...
696
Overview of Fatty Acid Metabolism01:28

Overview of Fatty Acid Metabolism

Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
36.9K
What is Metabolism?00:52

What is Metabolism?

Overview
131.7K
Bile01:19

Bile

Bile is a crucial bodily fluid, characterized by its yellow-green color and alkaline nature. Produced in the liver, it is transported through the common hepatic duct into either the cystic duct, leading to the gallbladder, or directly into the common bile duct. The flow of bile is regulated by the sphincter of Oddi located at the entrance of the duodenum. When this sphincter is closed, bile is redirected to the gallbladder for storage and concentration.
Bile is released when dietary fats enter...
4.2K
Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors01:13

Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors

Peptic ulcers, often induced by H. pylori infections or NSAID usage, arise from disruptions in the delicate balance of gastric acid production. Peptic ulcers stem from heightened gastric acid levels due to H. pylori infections or NSAID use. The protective mucus layer diminishes in the presence of these factors, allowing gastric acid to erode the stomach lining and form ulcers.
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
935
Prokaryotic Transcriptional Activators and Repressors01:58

Prokaryotic Transcriptional Activators and Repressors

The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
25.5K