GO:0035729 cellular response to hepatocyte growth factor stimulus: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035729 describes the cellular response to hepatocyte growth factor (HGF), a pleiotropic cytokine that regulates cell movement, secretion, enzyme production, and gene expression.
• HGF signaling is essential for liver regeneration, as genetic elimination of HGF compromises liver regeneration after partial hepatectomy.
• The cellular response to HGF involves activation of multiple transduction pathways, including those studied in pancreatic acini and c-Met signal transduction.
• HGF can induce morphogenesis without disrupting tight junction integrity in epithelial cells and promotes growth inhibition and apoptosis in liver myofibroblasts, aiding resolution from liver cirrhosis.
• In cancer, HGF enhances lung cancer cell migration via the α7 nicotinic acetylcholine receptor and phosphoinositide kinase-3-dependent pathway.
• Researchers study GO:0035729 using knockout, knock-in, and overexpression models, combined with CRISPR screening and bioinformatics to dissect signaling networks.
Description
The cellular response to hepatocyte growth factor stimulus (GO:0035729) encompasses all processes by which a cell changes its state or activity in response to hepatocyte growth factor (HGF). This includes alterations in movement, secretion, enzyme production, and gene expression. HGF is a multifunctional cytokine that plays critical roles in development, tissue regeneration, and cancer progression. Understanding this response is fundamental for researchers in cell biology, oncology, and regenerative medicine. The term is defined in the Gene Ontology as any process that results in a change in state or activity of a cell as a result of an HGF stimulus. HGF was initially identified as a mitogen for hepatocytes, and its effects on hepatocyte growth and liver regeneration have been demonstrated in transgenic mice. The signaling cascade triggered by HGF involves binding to its receptor c-Met, leading to activation of multiple downstream pathways. These pathways regulate diverse cellular outcomes, from morphogenesis to apoptosis, depending on cell type and context [4,5]. Given its broad impact, GO:0035729 is a key term for annotating gene products involved in HGF-mediated responses.
cellular response to hepatocyte growth factor stimulus At A Glance
| GO ID | GO:0035729 |
|---|---|
| GO term | cellular response to hepatocyte growth factor stimulus |
| Ontology | biological_process |
| Synonym | cellular response to HGF stimulus |
| Major function | Mediates cellular changes in movement, secretion, enzyme production, and gene expression in response to HGF |
| Related receptor | c-Met (MET) |
| Key pathways | PI3K/AKT, MAPK, and other transduction pathways [3,7] |
| Physiological roles | Liver regeneration, morphogenesis, apoptosis, cell migration [4,5,6,8] |
What Is GO:0035729?
GO:0035729, cellular response to hepatocyte growth factor stimulus, is defined as any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hepatocyte growth factor stimulus. This biological process captures the downstream cellular events triggered when HGF binds to its receptor, primarily c-Met, leading to signal transduction and functional changes. The synonym cellular response to HGF stimulus is also used.
Why Is cellular response to hepatocyte growth factor stimulus Important in Cell Biology?
GO:0035729 is important because HGF signaling is a central regulator of tissue homeostasis, regeneration, and disease. It is critical for liver regeneration after injury, as shown by compromised regeneration in HGF-deficient mice. Dysregulation of HGF/c-Met signaling is implicated in cancer progression, including enhanced migration of lung cancer cells. The pathway also influences cell survival and apoptosis in liver myofibroblasts, contributing to resolution of cirrhosis. Therefore, understanding this process aids in developing therapeutic strategies for liver diseases, cancer, and regenerative medicine.
• Essential for liver regeneration after partial hepatectomy.
• Regulates hepatocyte growth and gene expression in vivo.
• Activates multiple transduction pathways in pancreatic acini.
• Induces morphogenesis in epithelial cells without disrupting tight junctions.
• Promotes growth inhibition and apoptosis in liver myofibroblasts, aiding cirrhosis resolution.
• Enhances cancer cell migration, e.g., in lung cancer via α7 nAChR and PI3K.
• Involved in host-pathogen systems biology, such as Helicobacter pylori-induced c-Met signaling.
• Modulates response of primary hepatocytes to epidermal growth factor.
• Potential target for anti-fibrotic and anti-cancer therapies.
• Key for understanding cell motility, secretion, and enzyme production.
What Happens During cellular response to hepatocyte growth factor stimulus?
HGF Binding and Receptor Activation
In simple terms: HGF binds to its receptor on the cell surface, turning it on.
The cellular response to HGF begins with HGF binding to its high-affinity receptor, c-Met. This binding induces receptor dimerization and autophosphorylation, creating docking sites for adaptor proteins. This step is the initiating event for downstream signaling. In hepatocytes, HGF stimulation modulates the response to epidermal growth factor, indicating cross-talk between signaling pathways.
Activation of Intracellular Transduction Pathways
In simple terms: The activated receptor triggers a cascade of signaling molecules inside the cell.
Following receptor activation, multiple intracellular pathways are engaged, including the PI3K/AKT and MAPK cascades. In rat pancreatic acini, HGF activates several transduction pathways, demonstrating the pleiotropic nature of the response. Logical modeling of HGF and Helicobacter pylori-induced c-Met signaling has helped map these complex interactions.
Cellular Outcomes: Movement, Secretion, and Gene Expression
In simple terms: The cell changes its behavior, such as moving, secreting substances, or switching genes on/off.
Downstream signaling leads to diverse cellular responses. HGF induces MDCK cell morphogenesis without causing loss of tight junction functional integrity, showing effects on cell shape and movement. In liver myofibroblasts, HGF promotes growth inhibition and apoptosis, contributing to resolution from liver cirrhosis. In lung cancer cells, HGF enhances migration via the α7 nicotinic acetylcholine receptor and PI3K-dependent pathway. Additionally, HGF influences gene expression, as seen in transgenic mice where it affects hepatocyte growth and liver regeneration.
Regulation of Liver Regeneration
In simple terms: HGF is crucial for the liver to regrow after damage.
Conditional genetic elimination of HGF in mice compromises liver regeneration after partial hepatectomy, highlighting the essential role of HGF signaling in this process. This underscores the importance of GO:0035729 in tissue repair.
Key Genes Involved in GO:0035729 cellular response to hepatocyte growth factor stimulus
Key genes and proteins involved in the cellular response to hepatocyte growth factor stimulus include the ligand HGF, its receptor MET, and downstream signaling molecules.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HGF | Ligand that initiates the cellular response | Knockout models show impaired liver regeneration |
| MET | Receptor tyrosine kinase for HGF | Central to signal transduction; studied in logical models |
| PIK3CA | Catalytic subunit of PI3K, activates AKT pathway | Involved in HGF-mediated migration |
| AKT1 | Serine/threonine kinase, promotes survival and growth | Downstream effector of PI3K |
| MAPK1 | Mitogen-activated protein kinase, regulates proliferation | Activated by HGF in pancreatic acini |
| MAPK3 | Mitogen-activated protein kinase, regulates proliferation | Activated by HGF in pancreatic acini |
| CHRNA7 | α7 nicotinic acetylcholine receptor, enhances HGF-mediated migration | Studied in lung cancer cells |
| EGFR | Epidermal growth factor receptor, cross-talks with HGF signaling | Modulates hepatocyte response |
| STAT3 | Transcription factor, mediates gene expression changes | Downstream of HGF in various cells |
| SRC | Non-receptor tyrosine kinase, contributes to c-Met signaling | Part of c-Met signal transduction |
| GRB2 | Adaptor protein, links c-Met to RAS-MAPK pathway | Involved in HGF-induced signaling |
| GAB1 | Docking protein, amplifies c-Met signals | Key mediator of HGF responses |
| RAC1 | Rho GTPase, regulates cell migration and morphogenesis | Mediates HGF-induced morphogenesis |
| CDC42 | Rho GTPase, regulates cell polarity and migration | Involved in HGF-induced morphogenesis |
| PTK2 | Focal adhesion kinase, regulates cell motility | Downstream of HGF in migration |
| VIM | Vimentin, mesenchymal marker, associated with migration | Upregulated in HGF-treated cells |
| CDH1 | E-cadherin, maintains cell-cell adhesion | Tight junction integrity during HGF-induced morphogenesis |
| TJP1 | Tight junction protein 1, maintains barrier function | Preserved during HGF-induced morphogenesis |
How Is cellular response to hepatocyte growth factor stimulus Regulated?
The cellular response to HGF is tightly regulated at multiple levels. Receptor availability and activity are controlled by phosphorylation and internalization. Downstream, the PI3K/AKT and MAPK pathways are modulated by phosphatases and feedback loops. In liver myofibroblasts, HGF promotes apoptosis, which is a regulated process. The presence of HGF in the microenvironment, as shown in transgenic mice, influences hepatocyte growth and gene expression. Additionally, cross-talk with other signaling pathways, such as EGFR, modulates the response. In pathological conditions, Helicobacter pylori can modulate c-Met signaling, altering the cellular response.
cellular response to hepatocyte growth factor stimulus and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HGF | Liver cirrhosis, regeneration failure | HGF knockout mice |
| MET | Cancer, host-pathogen interactions | c-Met signaling models |
| CHRNA7 | Lung cancer metastasis | Lung cancer cell lines with nicotine treatment |
| PIK3CA | Cancer cell migration | PI3K inhibitors in migration assays |
| EGFR | Liver regeneration, cross-talk | Primary hepatocyte cultures |
Liver Cirrhosis and Fibrosis
HGF signaling promotes growth inhibition and apoptosis in liver myofibroblasts, leading to resolution from liver cirrhosis. This suggests that enhancing HGF response could be therapeutic for fibrotic liver diseases.
Liver Regeneration Failure
Conditional genetic elimination of HGF in mice compromises liver regeneration after partial hepatectomy, indicating that impaired HGF signaling contributes to regeneration failure.
Cancer Progression and Metastasis
HGF enhances lung cancer cell migration via the α7 nicotinic acetylcholine receptor and PI3K-dependent pathway. Dysregulated HGF/c-Met signaling is associated with tumor invasion and metastasis.
Host-Pathogen Interactions
Helicobacter pylori can modulate c-Met signal transduction, as shown by logical modeling, linking HGF signaling to gastric pathology.
From cellular response to hepatocyte growth factor stimulus-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does HGF drive liver regeneration in vivo? | HGF conditional knockout mice |
| How does HGF affect hepatocyte gene expression? | HGF transgenic mice |
| What pathways are activated by HGF in pancreatic cells? | Rat pancreatic acini |
| Does HGF induce morphogenesis without disrupting tight junctions? | MDCK cell model |
| How does HGF promote apoptosis in liver myofibroblasts? | Liver myofibroblast cultures |
| Does HGF enhance cancer cell migration via nAChR? | Lung cancer cell lines |
How to Study the cellular response to hepatocyte growth factor stimulus Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Gene expression changes | Identify HGF-induced transcriptional programs |
| Phosphoproteomics | Protein phosphorylation events | Map signaling pathways activated by HGF |
| Live-cell imaging | Cell movement and morphology | Study HGF-induced morphogenesis |
| CRISPR knockout screening | Gene essentiality for HGF response | Discover novel regulators of GO:0035729 |
| Apoptosis assays | Cell death | Measure HGF-induced apoptosis in myofibroblasts |
| Migration assays | Cell motility | Assess HGF-enhanced cancer cell migration |
| Western blot | Protein expression and phosphorylation | Validate signaling changes |
Transcriptomics and RNA-seq
RNA sequencing can measure global gene expression changes following HGF stimulation, as demonstrated in transgenic mice where HGF affects gene expression. This method identifies downstream targets of GO:0035729.
Phosphoproteomics
Phosphoproteomics allows comprehensive mapping of signaling pathways activated by HGF, such as PI3K/AKT and MAPK, which are known to be engaged [7,8]. It can reveal novel phosphorylation events in response to HGF.
Live-cell Imaging
Imaging techniques can track cell movement and morphogenesis in real time, as shown in MDCK cells where HGF induces morphogenesis without loss of tight junction integrity. This is useful for studying dynamic cellular responses.
CRISPR Screening
Genome-wide CRISPR knockout screens can identify genes essential for HGF-induced phenotypes, such as migration or survival. This unbiased approach can uncover new components of the cellular response to HGF.
How CRISPR Can Be Used to Study GO:0035729 cellular response to hepatocyte growth factor stimulus
Knockout
CRISPR knockout of HGF or MET can abolish the cellular response to HGF, mimicking genetic elimination studies in mice. This helps determine the requirement of specific genes for GO:0035729.
Point Mutation
Introducing point mutations in key signaling domains of MET or downstream effectors can dissect their specific roles in HGF response. For example, mutation of phosphorylation sites can prevent interaction with adaptor proteins.
Knock-in
Knock-in of reporter genes or tags into endogenous loci, such as HGF or MET, allows real-time monitoring of expression and localization during HGF response. This can be combined with live-cell imaging.
Overexpression
Overexpression of HGF or constitutively active MET can amplify the cellular response, useful for studying downstream effects and identifying potential therapeutic targets.
How EDITGENE Supports cellular response to hepatocyte growth factor stimulus Research
Researchers studying cellular response to hepatocyte growth factor stimulus-related genes often need to determine whether a candidate gene is causally involved in the response or is merely correlated. EDITGENE provides comprehensive CRISPR-based services to enable such functional studies.
Contact EDITGENE today to design your custom CRISPR model for cellular response to hepatocyte growth factor stimulus research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BCAR1 Knockout HEK293 Cell Line | EDJ-KQ1304 | Human | 9564 | Details Get a Quote |
| GCLM Knockout HEK293 Cell Line | EDJ-KQ1587 | Human | 2730 | Details Get a Quote |
| CASR Knockout HEK293 Cell Line | EDJ-KQ3089 | Human | 846 | Details Get a Quote |
| VIL1 Knockout HEK293 Cell Line | EDJ-KQ3560 | Human | 7429 | Details Get a Quote |
| GCLC Knockout HEK293 Cell Line | EDJ-KQ3948 | Human | 2729 | Details Get a Quote |
| LGMN Knockout HEK293 Cell Line | EDJ-KQ5551 | Human | 5641 | Details Get a Quote |
| APPL1 Knockout HEK293 Cell Line | EDJ-KQ8379 | Human | 26060 | Details Get a Quote |
| APPL2 Knockout HEK293 Cell Line | EDJ-KQ12397 | Human | 55198 | Details Get a Quote |
| NRP1 Knockout HEK293 Cell Line | EDJ-KQ14498 | Human | 8829 | Details Get a Quote |
| HGF Knockout HEK293 Cell Line | EDC07565 | Human | 3082 | Details Get a Quote |
| NRP1 Knockout A-549 Cell Line | EDJ-KQ17928 | Human | 8829 | Details Get a Quote |
| VIL1 Knockout HCT 116 Cell Line | EDJ-KQ24050 | Human | 7429 | Details Get a Quote |
| APPL2 Knockout A-549 Cell Line | EDJ-KQ41281 | Human | 55198 | Details Get a Quote |
| APPL2 Knockout HCT 116 Cell Line | EDJ-KQ41282 | Human | 55198 | Details Get a Quote |
| APPL2 Knockout HeLa Cell Line | EDJ-KQ41283 | Human | 55198 | Details Get a Quote |
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Frequently Asked Questions About cellular response to hepatocyte growth factor stimulus
What is GO:0035729?
GO:0035729 is the Gene Ontology term for cellular response to hepatocyte growth factor stimulus, defined as any process that results in a change in state or activity of a cell as a result of an HGF stimulus.
What genes are involved in cellular response to hepatocyte growth factor stimulus?
Key genes include HGF, MET, PIK3CA, AKT1, MAPK1, MAPK3, CHRNA7, and others involved in downstream signaling [3,7,8].
How does HGF affect liver regeneration?
HGF is critical for liver regeneration; conditional genetic elimination of HGF in mice compromises liver regeneration after partial hepatectomy.
What pathways are activated by HGF?
HGF activates multiple pathways including PI3K/AKT and MAPK, as shown in pancreatic acini and other cell types [7,8].
Does HGF cause loss of tight junctions?
No, HGF induces MDCK cell morphogenesis without causing loss of tight junction functional integrity.
How is HGF involved in cancer?
HGF enhances lung cancer cell migration via the α7 nicotinic acetylcholine receptor and PI3K-dependent pathway.
What is the role of HGF in liver cirrhosis?
HGF promotes growth inhibition and apoptosis in liver myofibroblasts, leading to resolution from liver cirrhosis.
Can CRISPR be used to study HGF signaling?
Yes, CRISPR knockout, knock-in, and overexpression models can be used to dissect gene function in the cellular response to HGF.
What model systems are used to study GO:0035729?
Common models include HGF transgenic mice, HGF knockout mice, MDCK cells, and primary hepatocyte cultures.
How does Helicobacter pylori interact with HGF signaling?
Helicobacter pylori can modulate c-Met signal transduction, as shown by logical modeling of HGF and H. pylori-induced c-Met signaling.
Conclusion
The cellular response to hepatocyte growth factor stimulus (GO:0035729) is a vital biological process with broad implications in liver regeneration, fibrosis, and cancer. Understanding its mechanisms through knockout, knock-in, and overexpression models, combined with CRISPR screening and bioinformatics, can reveal new therapeutic targets. EDITGENE provides the tools and expertise to accelerate this research.
References
- 1. Skouteris GG et al.. 1991. Hepatocyte conditioned medium modulates the response of primary rat hepatocyte cultures to epidermal growth factor.. Biochim Biophys Acta 1095(2):169-74 PMID: 1932136
- 2. Shiota G et al.. 1994. Hepatocyte growth factor in transgenic mice: effects on hepatocyte growth, liver regeneration and gene expression.. Hepatology 19(4):962-72 PMID: 8138271
- 3. Franke R et al.. 2008. Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction.. BMC Syst Biol 2:4 PMID: 18194572
- 4. Pollack AL et al.. 2004. Hepatocyte growth factor induces MDCK cell morphogenesis without causing loss of tight junction functional integrity.. Am J Physiol Cell Physiol 286(3):C482-94 PMID: 14592813
- 5. Kim WH et al.. 2005. Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis.. Am J Pathol 166(4):1017-28 PMID: 15793283
- 6. Nejak-Bowen K et al.. 2013. Conditional genetic elimination of hepatocyte growth factor in mice compromises liver regeneration after partial hepatectomy.. PLoS One 8(3):e59836 PMID: 23527275
- 7. Aparicio IM et al.. 2003. Hepatocyte growth factor activates several transduction pathways in rat pancreatic acini.. Biochim Biophys Acta 1643(1-3):37-46 PMID: 14654226
- 8. Yoneyama R et al.. 2016. Nicotine enhances hepatocyte growth factor-mediated lung cancer cell migration by activating the α7 nicotine acetylcholine receptor and phosphoinositide kinase-3-dependent pathway.. Oncol Lett 11(1):673-677 PMID: 26870265
