Related Experiment Video
Updated: Jun 9, 2025
09:16
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
7.2K
IGFALS suppresses hepatocellular carcinoma progression by stabilizing PPAR-γ
Le Xu1, Lin Xiong2, Yukai Chen1
1Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
International Immunopharmacology
|October 29, 2024
Summary
Insulin-like growth factor-binding protein 7 (IGFALS) suppresses hepatocellular carcinoma (HCC) by stabilizing PPAR-γ. This interaction upregulates HMGCS2, inhibiting tumor growth and progression.
Area of Science:
- Molecular oncology
- Biochemistry
- Cancer biology
Background:
- Insulin-like growth factor-binding protein 7 (IGFALS) regulates insulin-like growth factors (IGFs).
- Downregulation of IGFALS is observed in hepatocellular carcinoma (HCC) tissues and correlates with poor prognosis.
Purpose of the Study:
- To elucidate the molecular mechanism by which IGFALS inhibits HCC.
- To investigate IGFALS as a potential therapeutic target for HCC treatment.
Main Methods:
- Immunohistochemistry and bioinformatics analysis of clinical samples.
- In vitro cell-based assays (proliferation, invasion, migration, epithelial-mesenchymal transition).
- Gene Set Enrichment Analysis (GSEA), Western blotting, immunofluorescence, co-immunoprecipitation, mass spectrometry, and tumor xenograft models.
Main Results:
- IGFALS inhibits HCC cell proliferation, invasion, migration, and epithelial-mesenchymal transition.
- IGFALS binds to and stabilizes PPAR-γ via deubiquitination, promoting the PPAR-γ/HMGCS2 pathway.
- IGFALS facilitates PPAR-γ binding with USP9X, a deubiquitinating enzyme, enhancing PPAR-γ stability.
Conclusions:
- IGFALS suppresses hepatocellular carcinoma through the PPAR-γ/HMGCS2 signaling axis.
- IGFALS represents a promising therapeutic target for HCC treatment.
Related Concept Videos
01:16TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:24Liver Regeneration
3.2K
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...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.2K
01:09GPCRs Regulate Adenylyl Cylase Activity
5.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.3K
01:19Interactions Between Signaling Pathways
6.2K
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...
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...
6.2K
02:26NF-κB-dependent Signaling Pathway
7.2K
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...
NF-κB-dependent Signaling Mechanism
The...
7.2K