GO:1902202 regulation of hepatocyte growth factor receptor signaling pathway: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1902202 describes any process that modulates the frequency, rate, or extent of hepatocyte growth factor (HGF) receptor (MET) signaling.
• MET is a receptor tyrosine kinase activated by HGF, and its signaling is tightly regulated in normal development and tissue repair.
• Dysregulated MET signaling drives tumorigenesis, metastasis, and drug resistance in many cancers, making it a major therapeutic target.
• Regulation occurs at multiple levels, including ligand availability, receptor trafficking, and intracellular sorting by proteins such as sorting nexins.
• Experimental models for studying GO:1902202 include knockout mice, point-mutant cell lines, and knock-in reporters.
• CRISPR-based editing enables precise interrogation of genes that regulate HGF/MET signaling in disease models.
Description
The hepatocyte growth factor receptor (MET) signaling pathway is a critical regulator of cell proliferation, survival, migration, and morphogenesis during development and tissue repair. The Gene Ontology term GO:1902202, regulation of hepatocyte growth factor receptor signaling pathway, encompasses any process that modulates the frequency, rate, or extent of MET signaling. This term is essential for researchers studying how cells control MET activity in normal physiology and how its dysregulation contributes to diseases such as cancer and fibrosis. Understanding the regulatory mechanisms of MET signaling is crucial for developing targeted therapies, as aberrant MET activation is implicated in tumor progression, metastasis, and resistance to conventional treatments. Moreover, recent studies have highlighted the importance of spatiotemporal regulation of MET by intracellular trafficking proteins, such as sorting nexins, in colorectal cancer cells. This article provides a comprehensive overview of GO:1902202, covering its definition, biological significance, key genes, regulatory mechanisms, disease associations, and experimental approaches for investigation.
regulation of hepatocyte growth factor receptor signaling pathway At A Glance
| GO ID | GO:1902202 |
|---|---|
| GO term | regulation of hepatocyte growth factor receptor signaling pathway |
| Ontology | biological_process |
| Synonym | regulation of HGF receptor signaling pathway; regulation of HGF receptor signalling pathway; regulation of Met signaling pathway |
| Major function | Modulates the frequency, rate, or extent of HGF/MET signaling |
| Key ligand | Hepatocyte growth factor (HGF) |
| Key receptor | MET (c-Met), a receptor tyrosine kinase |
| Associated diseases | Cancers (e.g., renal cell carcinoma, glioblastoma, colorectal cancer), liver fibrosis |
| Research models | Knockout mice, point-mutant cell lines, knock-in reporters, CRISPR screens |
What Is GO:1902202?
GO:1902202 is defined as any process that modulates the frequency, rate, or extent of the hepatocyte growth factor receptor signaling pathway. In simpler terms, it includes all cellular mechanisms that turn up or down the signals triggered when HGF binds to its receptor MET. This regulation can occur at various steps, from ligand availability and receptor activation to downstream signaling and receptor degradation.
Why Is regulation of hepatocyte growth factor receptor signaling pathway Important in Cell Biology?
Regulation of HGF/MET signaling is vital for normal embryonic development, tissue regeneration, and wound healing, but its dysregulation is a hallmark of many cancers and fibrotic diseases. Understanding GO:1902202 provides insights into how cells maintain signaling homeostasis and how disruptions lead to pathological conditions, thereby informing the development of targeted therapeutics.
• Controls cell proliferation, survival, and migration during development and tissue repair.
• Dysregulation is implicated in tumorigenesis, metastasis, and angiogenesis in multiple cancers.
• MET signaling is a key driver of resistance to EGFR inhibitors and other targeted therapies.
• Regulation of MET trafficking by sorting nexins affects cancer cell behavior.
• HGF/MET axis is a therapeutic target in bone metastases and renal cell carcinoma.
• Neuropilin-1 interaction with HGF/MET modulates liver fibrosis progression.
• Cyclic peptide-based biologics can regulate HGF-MET signaling for therapeutic benefit.
• Understanding regulation aids in designing CRISPR-based models for drug discovery.
• GO:1902202 helps annotate gene functions in signaling networks.
• Provides a framework for studying spatiotemporal control of receptor tyrosine kinases.
What Happens During regulation of hepatocyte growth factor receptor signaling pathway?
Ligand Availability and Receptor Activation
In simple terms: HGF must be present and bind to MET to start the signal.
Hepatocyte growth factor (HGF) is secreted by mesenchymal cells and binds to the MET receptor on epithelial cells, inducing receptor dimerization and autophosphorylation. Regulation of HGF availability, such as through proteolytic activation or sequestration by extracellular matrix, modulates the initiation of MET signaling.
Receptor Trafficking and Sorting
In simple terms: After activation, MET is moved around inside the cell to control how long the signal lasts.
Following activation, MET is internalized and sorted into endosomes. Sorting nexins 1 and 2 (SNX1/2) regulate the spatiotemporal activity of MET by directing it to degradation or recycling pathways, thereby controlling signal duration. This trafficking is crucial for attenuating or prolonging downstream signals.
Downstream Signaling Cascades
In simple terms: MET sends signals through several pathways that tell the cell to grow or survive.
Activated MET recruits adaptor proteins like GAB1 and activates downstream pathways including PI3K/AKT, RAS/MAPK, and STAT3, which promote cell proliferation, survival, and migration. Regulation of these cascades occurs through phosphatases, feedback loops, and cross-talk with other receptors.
Negative Feedback and Degradation
In simple terms: Cells have brakes to stop MET signaling, such as degrading the receptor.
Negative regulators include the E3 ubiquitin ligase CBL, which ubiquitinates MET and targets it for degradation, and protein tyrosine phosphatases that dephosphorylate MET. These mechanisms prevent excessive signaling and are often disrupted in cancer.
Key Genes Involved in GO:1902202 regulation of hepatocyte growth factor receptor signaling pathway
The following genes and proteins are key players in the regulation of HGF/MET signaling (GO:1902202).
| Gene | Major Role | Research Relevance |
|---|---|---|
| HGF | Ligand for MET receptor | Activates MET signaling; studied in tissue repair and cancer |
| MET | Receptor tyrosine kinase | Central to pathway; mutations and overexpression in cancers |
| GAB1 | Adaptor protein | Recruits downstream effectors; essential for MET signaling |
| SNX1 | Sorting nexin | Regulates endosomal sorting of MET; affects signaling duration |
| SNX2 | Sorting nexin | Works with SNX1 to control MET trafficking |
| CBL | E3 ubiquitin ligase | Negative regulator; targets MET for degradation |
| NRP1 | Neuropilin-1 | Modulates HGF/MET signaling in liver fibrosis |
| PIK3CA | PI3K catalytic subunit | Mediates downstream AKT signaling |
| AKT1 | Serine/threonine kinase | Promotes survival; downstream of MET |
| MAPK1 | ERK2 | Transmits proliferative signals from MET |
| STAT3 | Transcription factor | Mediates gene expression changes downstream of MET |
| SRC | Non-receptor tyrosine kinase | Potentiates MET signaling and cross-talk |
| PTEN | Phosphatase | Negative regulator of PI3K/AKT; counteracts MET signaling |
| PTPN11 | SHP2 phosphatase | Positive regulator of RAS/MAPK downstream of MET |
| CDH1 | E-cadherin | Affects MET localization and signaling |
| EGFR | Receptor tyrosine kinase | Cross-talks with MET; co-targeting strategies |
| VEGFA | Vascular endothelial growth factor | Induced by MET signaling; promotes angiogenesis |
How Is regulation of hepatocyte growth factor receptor signaling pathway Regulated?
Regulation of HGF/MET signaling (GO:1902202) occurs at multiple levels. Ligand availability is controlled by proteases and extracellular matrix binding. Receptor activity is modulated by phosphorylation/dephosphorylation, ubiquitination, and endocytic trafficking. Downstream signaling is regulated by feedback loops, phosphatases (e.g., PTEN), and cross-talk with other pathways. Additionally, microRNAs and epigenetic mechanisms can influence MET expression.
regulation of hepatocyte growth factor receptor signaling pathway and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MET | Renal cell carcinoma, glioblastoma | MET knockout or point-mutant cell lines |
| HGF | Cancer progression, tissue repair | HGF overexpression or knockout mice |
| NRP1 | Liver fibrosis | Hepatocyte-specific NRP-1 knockout mice |
| SNX1/2 | Colorectal cancer | SNX1/2 knockout HCT116 cells |
| MET | Bone metastases | Bone metastasis mouse models with MET inhibitors |
Cancer
Dysregulated HGF/MET signaling is a driver of tumorigenesis, metastasis, and angiogenesis in many cancers, including renal cell carcinoma, glioblastoma, and colorectal cancer. MET amplification or mutation leads to constitutive activation, promoting cell proliferation and survival. Targeting the HGF/MET axis is a therapeutic strategy, with inhibitors and antibodies in clinical trials.
Liver Fibrosis
HGF/MET signaling plays a role in liver regeneration and fibrosis. Interaction between neuropilin-1 and HGF/MET pathway modulates liver fibrosis progression, as shown in hepatocyte-specific NRP-1 knockout mice. Regulation of this pathway may offer therapeutic avenues for fibrotic liver diseases.
Bone Metastases
The HGF/c-Met axis is implicated in bone metastases, where it promotes tumor cell homing to bone and osteolysis. Targeting this pathway is being explored to prevent or treat bone metastases in cancers such as prostate and breast cancer.
From regulation of hepatocyte growth factor receptor signaling pathway-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of MET affect tumor growth? | MET knockout cell lines or mice |
| How do point mutations in MET alter signaling? | Point-mutant MET knock-in cell lines |
| Can we visualize MET trafficking in live cells? | Tagged MET knock-in (e.g., GFP) |
| What is the effect of HGF overexpression? | HGF overexpression transgenic mice |
| Which genes regulate MET signaling? | CRISPR library screening in cancer cell lines |
| Does NRP1 regulate HGF/MET in liver fibrosis? | Hepatocyte-specific NRP-1 knockout mice |
How to Study the regulation of hepatocyte growth factor receptor signaling pathway Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screening | Gene essentiality for MET signaling | Identify novel regulators |
| Phosphoproteomics | Phosphorylation changes | Map signaling networks |
| Live-cell imaging | Receptor trafficking dynamics | Study SNX1/2 effects |
| RNA-seq | Transcriptional changes | Discover downstream targets |
| Western blot | Protein expression and phosphorylation | Validate MET activation |
| Immunoprecipitation | Protein-protein interactions | Identify MET complexes |
| Flow cytometry | Cell surface MET levels | Quantify receptor internalization |
| Organoid culture | 3D growth and signaling | Model tissue-specific regulation |
CRISPR Screening
Genome-wide CRISPR knockout or activation screens can identify regulators of HGF/MET signaling. For example, screens in HCT116 colorectal cancer cells revealed roles for sorting nexins in MET trafficking.
Phosphoproteomics
Mass spectrometry-based phosphoproteomics quantifies changes in MET phosphorylation and downstream signaling upon genetic or pharmacological perturbations.
Live-Cell Imaging
Tagged MET (e.g., GFP) allows real-time visualization of receptor internalization, trafficking, and recycling in response to HGF.
RNA Sequencing
Transcriptomic profiling identifies gene expression changes downstream of MET activation or inhibition, revealing feedback mechanisms and biomarkers.
How CRISPR Can Be Used to Study GO:1902202 regulation of hepatocyte growth factor receptor signaling pathway
Knockout
CRISPR knockout of MET or its regulators (e.g., SNX1/2) in cell lines or mice ablates protein function, revealing their roles in HGF/MET signaling and disease phenotypes.
Point Mutation
Introducing specific point mutations (e.g., kinase-dead MET) via CRISPR allows dissection of catalytic and docking functions in signaling.
Knock-in
Knock-in of tagged MET (e.g., GFP) enables live-cell imaging and proteomic analysis of receptor dynamics and interactions.
Overexpression
CRISPR activation or transgenic overexpression of HGF or MET can model ligand-driven tumorigenesis and identify downstream effects.
How EDITGENE Supports regulation of hepatocyte growth factor receptor signaling pathway Research
Researchers studying regulation of hepatocyte growth factor receptor signaling pathway-related genes often need to determine whether a candidate gene is causally involved in pathway regulation or disease. EDITGENE provides comprehensive CRISPR-based services to create precise cellular and animal models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for regulation of hepatocyte growth factor receptor signaling pathway research.
Frequently Asked Questions About regulation of hepatocyte growth factor receptor signaling pathway
What is GO:1902202?
GO:1902202 is a Gene Ontology term for any process that modulates the frequency, rate, or extent of hepatocyte growth factor receptor signaling pathway.
What genes are involved in regulation of hepatocyte growth factor receptor signaling pathway?
Key genes include HGF, MET, GAB1, SNX1, SNX2, CBL, and NRP1, among others.
How is HGF/MET signaling regulated?
It is regulated at multiple levels, including ligand availability, receptor trafficking by sorting nexins, downstream feedback, and degradation.
What diseases are associated with dysregulated HGF/MET signaling?
Cancers such as renal cell carcinoma, glioblastoma, and colorectal cancer, as well as liver fibrosis and bone metastases.
What experimental models are used to study GO:1902202?
Knockout mice, point-mutant cell lines, knock-in reporters, and CRISPR screens are commonly used.
How can CRISPR help study regulation of HGF/MET signaling?
CRISPR enables knockout, point mutation, knock-in, and overexpression of genes to dissect their roles in the pathway.
What is the role of sorting nexins in MET signaling?
Sorting nexins 1 and 2 regulate endosomal sorting of MET, affecting signal duration and cellular responses.
Is MET a therapeutic target?
Yes, MET and HGF are therapeutic targets in various cancers, with inhibitors and antibodies in clinical development.
What is the connection between NRP1 and HGF/MET in liver fibrosis?
Neuropilin-1 interacts with HGF/MET to modulate liver fibrosis progression, as shown in hepatocyte-specific NRP-1 knockout mice.
How can EDITGENE help with my research on HGF/MET signaling?
EDITGENE offers CRISPR knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services to create custom models for studying this pathway.
Conclusion
GO:1902202, regulation of hepatocyte growth factor receptor signaling pathway, is a critical biological process that controls diverse cellular functions and is implicated in major diseases. Understanding its mechanisms through CRISPR-based models and advanced methodologies can accelerate therapeutic development. EDITGENE provides the tools and expertise to investigate this pathway with precision.
References
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- 2. Whang YM et al.. 2019. Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases.. Int J Mol Sci 20(2) PMID: 30658428
- 3. Galimi F et al.. 1993. The hepatocyte growth factor and its receptor.. Stem Cells 11 Suppl 2:22-30 PMID: 8401259
- 4. De Silva DM et al.. 2017. Targeting the hepatocyte growth factor/Met pathway in cancer.. Biochem Soc Trans 45(4):855-870 PMID: 28673936
- 5. Harshman LC et al.. 2013. Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma.. Cancer J 19(4):316-23 PMID: 23867513
- 6. Wallace GC 4th et al.. 2013. Targeting oncogenic ALK and MET: a promising therapeutic strategy for glioblastoma.. Metab Brain Dis 28(3):355-66 PMID: 23543207
- 7. Ding H et al.. 2025. Interaction of neuropilin-1 and hepatocyte growth factor/C-Met pathway in liver fibrosis progression in hepatocyte-specific NRP-1 knockout mice.. J Gastroenterol 60(8):1000-1013 PMID: 40419692
- 8. Sato H et al.. 2020. Cyclic Peptide-Based Biologics Regulating HGF-MET.. Int J Mol Sci 21(21) PMID: 33121208
