GO:0010718 positive regulation of epithelial to mesenchymal transition: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010718 describes any process that increases the rate, frequency, or extent of epithelial to mesenchymal transition (EMT), a developmental and pathological program in which epithelial cells lose polarity and adhesion and become migratory mesenchymal cells.
• Positive regulation of EMT is driven by transcription factors such as SNAI1, by epigenetic modifiers such as EZH2, and by microenvironmental signals including hypoxia and inflammatory cytokines.
• HIF-1α networks, inflammatory cytokine signaling, and epigenetic reprogramming converge to activate EMT-associated gene expression programs.
• EMT induction is linked to cancer stem cell generation, therapy resistance, and fibrosis, making it a major target for mechanistic and translational studies.
• Key marker changes include loss of E-cadherin, gain of vimentin, and upregulation of mesenchymal effectors such as FAM64A and ITGβ3.
• CRISPR-based knockout, point mutation, knock-in, and overexpression models enable causal testing of EMT regulators in relevant cell backgrounds.
Description
GO:0010718, positive regulation of epithelial to mesenchymal transition, is a biological process term that captures any mechanism increasing the rate, frequency, or extent of EMT. EMT itself is a cellular program in which epithelial cells lose apical/basolateral polarity, sever intercellular adhesive junctions, degrade basement membrane components, and adopt a migratory mesenchymal phenotype. Because this process is central to development, wound healing, fibrosis, and cancer progression, understanding its positive regulators is a high-priority research area. Positive regulation of EMT is not a single linear pathway but a convergence of transcriptional, epigenetic, and microenvironmental inputs. Hypoxia, inflammatory cytokines, and epigenetic enzymes such as EZH2 can each enhance EMT gene expression programs. Transcription factors such as SNAI1 directly regulate EMT-associated genes in cancer stem cells, while additional effectors such as FAM64A and ITGβ3 modulate mesenchymal features and therapy response. This article integrates the QuickGO definition with verified PubMed literature to outline the mechanisms, key genes, disease links, and experimental models used to study positive regulation of EMT.
positive regulation of epithelial to mesenchymal transition At A Glance
| GO ID | GO:0010718 |
|---|---|
| GO term | positive regulation of epithelial to mesenchymal transition |
| Ontology | biological_process |
| Synonym | none |
| Major function | Increases the rate, frequency, or extent of epithelial to mesenchymal transition |
| Definition source | QuickGO definition: Any process that increases the rate, frequency, or extent of epithelial to mesenchymal transition. Epithelial to mesenchymal transition is where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell. |
| Related processes | Hypoxia response, inflammatory cytokine signaling, epigenetic regulation, cancer stem cell generation |
| Representative regulators | HIF-1α network, SNAI1, EZH2, FAM64A, ITGβ3, vimentin |
| Disease relevance | Cancer progression, fibrosis, therapy resistance |
What Is GO:0010718?
In our own words, GO:0010718 refers to any biological process that increases the rate, frequency, or extent of epithelial to mesenchymal transition. It includes signals and molecular events that promote the loss of epithelial polarity and adhesion and the acquisition of a migratory mesenchymal state, as defined by QuickGO.
Why Is positive regulation of epithelial to mesenchymal transition Important in Cell Biology?
Positive regulation of EMT is important because it controls a reversible cellular state change that underlies normal development but also drives pathological processes such as tumor invasion, metastasis, and organ fibrosis. Identifying the positive regulators of EMT provides mechanistic insight into disease progression and reveals candidate targets for therapeutic intervention.
• Controls developmental EMT programs required for tissue morphogenesis.
• Promotes cancer cell migration, invasion, and metastatic dissemination.
• Contributes to cancer stem cell generation and stemness features.
• Mediates therapy resistance, including trastuzumab resistance in HER2-positive breast cancer.
• Drives fibrosis after acute kidney injury through EZH2-dependent mechanisms.
• Integrates hypoxia and inflammatory cytokine signals into EMT gene expression.
• Involves epigenetic reprogramming that can be targeted experimentally.
• Serves as a readout for CRISPR-based functional studies of EMT regulators.
• Links extracellular matrix remodeling and basement membrane degradation to cell motility.
• Provides biomarkers such as vimentin and E-cadherin changes for EMT monitoring.
What Happens During positive regulation of epithelial to mesenchymal transition?
Initiation by microenvironmental signals
In simple terms: Outside signals such as low oxygen or inflammation can start the EMT program.
Positive regulation of EMT can be initiated by microenvironmental cues including hypoxia and inflammatory cytokines. Hypoxia activates the HIF-1α network, which regulates EMT in low-oxygen conditions. Inflammatory cytokine-induced EMT involves epigenetic regulation and can promote cancer stem cell generation. These signals increase the rate and extent of EMT by activating downstream transcriptional programs.
Transcriptional activation of EMT genes
In simple terms: Master transcription factors switch on genes that change the cell's identity.
Transcription factors such as SNAI1 mediate transcriptional regulation of EMT genes in breast cancer stem cells. Lipopolysaccharide can transcriptionally regulate EMT-related genes in cervical cancer cells. These transcriptional events increase expression of mesenchymal markers and repress epithelial adhesion molecules, thereby promoting the mesenchymal state.
Epigenetic remodeling
In simple terms: Chemical marks on DNA and histones can lock in the EMT program.
Epigenetic regulators such as EZH2 promote renal fibrosis after acute kidney injury by inducing EMT and activating M2 macrophage polarization. Epigenetic regulation is also implicated in inflammatory cytokine-induced EMT and cancer stem cell generation. Such remodeling increases the persistence and extent of EMT gene expression.
Cytoskeletal and adhesion changes
In simple terms: The cell changes its skeleton and sticky junctions to become mobile.
EMT involves loss of apical/basolateral polarity, severing of intercellular adhesive junctions, and degradation of basement membrane components, as defined by QuickGO. Vimentin, a mesenchymal cytoskeletal protein, is regulated in pathogenesis and serves as a marker of the mesenchymal state. These structural changes enable migratory behavior.
Acquisition of stemness and therapy resistance
In simple terms: Cells that undergo EMT can become more stem-like and harder to treat.
Positive regulation of EMT is linked to stemness features; FAM64A up-regulation promotes EMT and enhances stemness in breast cancer cells. Targeting ITGβ3 can overcome trastuzumab resistance through EMT regulation in HER2-positive breast cancer. Thus, positive EMT regulators can contribute to cancer stem cell phenotypes and treatment failure.
Key Genes Involved in GO:0010718 positive regulation of epithelial to mesenchymal transition
The following genes and proteins have been experimentally implicated in positive regulation of epithelial to mesenchymal transition in the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HIF-1α | Hypoxia-induced regulator of EMT network | Studied in hypoxia-driven EMT models |
| SNAI1 | Transcriptional regulator of EMT genes | Breast cancer stem cell EMT studies |
| EZH2 | Epigenetic modifier promoting EMT and fibrosis | Renal fibrosis after acute kidney injury |
| FAM64A | Promotes EMT and stemness features | Breast cancer cell EMT and stemness assays |
| ITGβ3 | Integrin involved in EMT and therapy resistance | HER2-positive breast cancer trastuzumab resistance |
| Vimentin | Mesenchymal cytoskeletal marker | EMT marker and pathogenesis studies |
| E-cadherin | Epithelial adhesion protein lost during EMT | EMT marker in cancer and fibrosis models |
| Inflammatory cytokines | Induce EMT and cancer stem cell generation | Epigenetic regulation studies |
| LPS-responsive genes | Transcriptional regulation of EMT-related genes | Cervical cancer HeLa cell studies |
| M2 macrophage polarization markers | Linked to EZH2-mediated EMT in fibrosis | Acute kidney injury fibrosis models |
| HIF-1α network components | Oxygen-sensing EMT regulation | Hypoxia EMT studies |
| SNAI1 target EMT genes | Transcriptional EMT program | Breast cancer stem cell research |
| FAM64A downstream effectors | Stemness and EMT phenotype | Breast cancer cell models |
| ITGβ3 signaling components | Therapy resistance and EMT | HER2-positive breast cancer models |
| Vimentin regulatory pathways | Cytoskeletal remodeling in EMT | Pathogenesis studies |
| EZH2 epigenetic targets | Fibrosis and EMT gene expression | Kidney fibrosis models |
| Cytokine-induced epigenetic modifiers | EMT and stemness | Cancer stem cell generation studies |
How Is positive regulation of epithelial to mesenchymal transition Regulated?
Positive regulation of EMT is controlled by multiple layers of regulation. Hypoxia regulates EMT through the HIF-1α network. Inflammatory cytokines regulate EMT via epigenetic mechanisms and can induce cancer stem cell generation. EZH2 promotes EMT and fibrosis after acute kidney injury. SNAI1 transcriptionally regulates EMT genes in breast cancer stem cells. These regulatory inputs collectively increase the rate, frequency, or extent of EMT.
positive regulation of epithelial to mesenchymal transition and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| EZH2 | Renal fibrosis after acute kidney injury | Kidney injury mouse models and EMT assays |
| ITGβ3 | HER2-positive breast cancer trastuzumab resistance | HER2-positive breast cancer cell lines |
| FAM64A | Breast cancer EMT and stemness | Breast cancer cell lines and stemness assays |
| SNAI1 | Breast cancer stem cell EMT | Breast cancer stem cell models |
| HIF-1α | Hypoxia-driven EMT in cancer | Hypoxia cell culture and tumor models |
Cancer progression and metastasis
Positive regulation of EMT is strongly associated with cancer progression. FAM64A up-regulation promotes EMT and enhances stemness in breast cancer cells. ITGβ3 targeting overcomes trastuzumab resistance through EMT regulation in HER2-positive breast cancer. SNAI1-mediated transcriptional regulation of EMT genes occurs in breast cancer stem cells. These findings link positive EMT regulators to invasion, stemness, and therapy resistance.
Renal fibrosis after acute kidney injury
EZH2 promotes renal fibrosis after acute kidney injury by inducing EMT and activating M2 macrophage polarization. This demonstrates that positive regulation of EMT contributes to fibrotic disease progression in the kidney.
Inflammation-associated cancer
Inflammatory cytokine-induced EMT involves epigenetic regulation and cancer stem cell generation. Lipopolysaccharide transcriptionally regulates EMT-related genes in cervical cancer cells. These studies connect inflammatory signaling to positive regulation of EMT in cancer.
Hypoxia-associated tumor biology
Hypoxia regulates EMT through the HIF-1α network. This provides a mechanism by which low-oxygen tumor microenvironments can positively regulate EMT and promote aggressive cancer phenotypes.
From positive regulation of epithelial to mesenchymal transition-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a candidate gene reduce EMT? | CRISPR knockout in epithelial cancer cell lines |
| Does a specific mutation alter EMT regulation? | CRISPR point mutation knock-in |
| Does tagging a protein affect its EMT regulatory function? | Tagged knock-in |
| Does overexpression of a gene induce EMT? | CRISPR overexpression or cDNA overexpression |
| Which epigenetic regulators control EMT? | Knockout of EZH2 or other epigenetic modifiers |
| How does hypoxia regulate EMT? | HIF-1α pathway perturbation under hypoxia |
How to Study the positive regulation of epithelial to mesenchymal transition Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global transcript changes | EMT gene expression profiling |
| qPCR | Specific EMT marker transcripts | Validation of EMT induction |
| Western blot | Protein levels of EMT markers | E-cadherin and vimentin changes |
| Immunofluorescence | Cellular localization of EMT proteins | Polarity and cytoskeleton studies |
| ChIP | Epigenetic factor binding | EZH2-mediated EMT regulation |
| Migration assay | Cell motility | Functional EMT outcome |
| Invasion assay | Basement membrane degradation | Metastatic potential |
| Stemness assay | Cancer stem cell features | EMT-stemness link |
Transcriptional profiling of EMT genes
RNA-seq and targeted gene expression assays can measure changes in EMT-related transcripts after perturbation. SNAI1-mediated transcriptional regulation of EMT genes has been studied in breast cancer stem cells, and lipopolysaccharide-induced transcriptional regulation of EMT-related genes has been examined in HeLa cells.
Epigenetic and chromatin assays
Chromatin immunoprecipitation and related methods can assess epigenetic regulation of EMT. EZH2 promotes EMT in renal fibrosis, and epigenetic regulation of inflammatory cytokine-induced EMT has been described.
Protein and marker analysis
Western blot and immunofluorescence can detect marker changes such as vimentin upregulation and E-cadherin loss. Vimentin regulation and pathogenesis have been reviewed, and ITGβ3-related EMT changes have been studied in breast cancer.
Functional migration and invasion assays
Migration and invasion assays measure the phenotypic outcome of positive EMT regulation. FAM64A promotes EMT and stemness features in breast cancer cells, and hypoxia regulates EMT through HIF-1α.
How CRISPR Can Be Used to Study GO:0010718 positive regulation of epithelial to mesenchymal transition
Knockout
CRISPR knockout can delete candidate positive regulators of EMT to test whether their loss reduces EMT. For example, knocking out EZH2 could test its role in renal fibrosis-associated EMT, and knocking out SNAI1 could test its role in breast cancer stem cell EMT.
Point Mutation
CRISPR point mutation can introduce specific amino acid changes to dissect domain functions in EMT regulators. This approach can test whether particular residues in transcription factors or epigenetic enzymes are required for positive regulation of EMT.
Knock-in
Knock-in of tags or reporters allows tracking of EMT regulators at endogenous loci. Tagged knock-in of vimentin or other markers can monitor EMT dynamics in live cells.
Overexpression
CRISPR overexpression can force expression of candidate genes to test sufficiency for EMT induction. Overexpression of FAM64A promotes EMT and stemness in breast cancer cells, and overexpression of ITGβ3-related pathways can modulate therapy resistance.
How EDITGENE Supports positive regulation of epithelial to mesenchymal transition Research
Researchers studying positive regulation of epithelial to mesenchymal transition-related genes often need to determine whether a candidate gene is causally involved in EMT initiation, maintenance, or reversal. EDITGENE provides CRISPR-based cell model services to enable such causal experiments.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of epithelial to mesenchymal transition research.
Frequently Asked Questions About positive regulation of epithelial to mesenchymal transition
What is GO:0010718?
GO:0010718 is the Gene Ontology term for positive regulation of epithelial to mesenchymal transition, defined as any process that increases the rate, frequency, or extent of EMT.
What is positive regulation of epithelial to mesenchymal transition?
It is the biological process that enhances EMT, in which epithelial cells lose polarity and adhesion and become migratory mesenchymal cells.
What genes are involved in positive regulation of epithelial to mesenchymal transition?
Genes and proteins include HIF-1α network components, SNAI1, EZH2, FAM64A, ITGβ3, and vimentin.
How is EMT positively regulated in cancer?
Hypoxia, inflammatory cytokines, epigenetic modifiers such as EZH2, and transcription factors such as SNAI1 can positively regulate EMT in cancer.
What is the role of EZH2 in EMT?
EZH2 promotes renal fibrosis after acute kidney injury by inducing EMT and activating M2 macrophage polarization.
How does hypoxia regulate EMT?
Hypoxia regulates EMT through the HIF-1α network.
What markers change during EMT?
EMT involves loss of E-cadherin and gain of mesenchymal markers such as vimentin.
How can CRISPR be used to study EMT regulators?
CRISPR knockout, point mutation, knock-in, and overexpression can test causal roles of candidate genes in EMT.
What diseases are linked to positive regulation of EMT?
Cancer progression, therapy resistance, and renal fibrosis are linked to positive regulation of EMT.
What experimental models are used for EMT research?
Common models include epithelial cancer cell lines, hypoxia culture, kidney injury models, and CRISPR-engineered cells.
Conclusion
GO:0010718 positive regulation of epithelial to mesenchymal transition is a central biological process that integrates hypoxia, inflammatory, transcriptional, and epigenetic inputs to promote a migratory mesenchymal state. The verified literature highlights key regulators such as HIF-1α, SNAI1, EZH2, FAM64A, ITGβ3, and vimentin in cancer and fibrosis contexts. CRISPR-based models provide powerful tools to test causality and identify new therapeutic targets in this process.
References
- 1. Wang HY et al.. 2022. Regulation of epithelial-to-mesenchymal transition in hypoxia by the HIF-1α network.. FEBS Lett 596(3):338-349 PMID: 34905218
- 2. Markopoulos GS et al.. 2019. Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation.. Cells 8(10) PMID: 31557902
- 3. Zhou X et al.. 2023. Enhancer of zeste homolog 2 promotes renal fibrosis after acute kidney injury by inducing epithelial-mesenchymal transition and activation of M2 macrophage polarization.. Cell Death Dis 14(4):253 PMID: 37029114
- 4. Singh D et al.. 2021. SNAI1-mediated transcriptional regulation of epithelial-to-mesenchymal transition genes in breast cancer stem cells.. Cell Signal 87:110151 PMID: 34537302
- 5. Zhang J et al.. 2019. Up-regulation of FAM64A promotes epithelial-to-mesenchymal transition and enhances stemness features in breast cancer cells.. Biochem Biophys Res Commun 513(2):472-478 PMID: 30979502
- 6. Boz Er AB et al.. 2024. Targeting ITGβ3 to Overcome Trastuzumab Resistance through Epithelial-Mesenchymal Transition Regulation in HER2-Positive Breast Cancer.. Int J Mol Sci 25(16) PMID: 39201327
- 7. Tavakolian S et al.. 2019. Transcriptional Regulation of Epithelial to Mesenchymal Transition Related Genes by Lipopolysaccharide in Human Cervical Cancer Cell Line HeLa.. Asian Pac J Cancer Prev 20(8):2455-2461 PMID: 31450920
- 8. Paulin D et al.. 2022. Vimentin: Regulation and pathogenesis.. Biochimie 197:96-112 PMID: 35151830
