GO:0007162 negative regulation of cell adhesion: Signaling Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0007162 (negative regulation of cell adhesion) describes any process that stops, prevents, or reduces the frequency, rate, or extent of cell adhesion.
• It is a biological_process that controls both cell-cell and cell-matrix interactions, often through adhesion receptor inhibition or downstream signaling.
• Key molecular players include CD43, OLA1, Rho GTPases, CD151, and EpCAM, which modulate adhesion strength and dynamics.
• Dysregulation of negative regulation of cell adhesion contributes to cancer metastasis, immune disorders, and developmental defects.
• Experimental approaches include CRISPR knockout, point mutation, knock-in, overexpression, and library screening to dissect gene function.
• Understanding this process aids in identifying therapeutic targets for diseases where cell adhesion is aberrant.
Description
Cell adhesion is fundamental for tissue architecture, cell migration, and signaling. Negative regulation of cell adhesion (GO:0007162) encompasses processes that reduce or inhibit adhesion, allowing cells to detach, migrate, or avoid inappropriate interactions. This regulation is critical for development, immune responses, and cancer progression. Researchers study this term to understand how cells dynamically control adhesion and to identify targets for therapeutic intervention.
negative regulation of cell adhesion At A Glance
| GO ID | GO:0007162 |
|---|---|
| GO term | negative regulation of cell adhesion |
| Ontology | biological_process |
| Synonym | cell adhesion receptor inhibitor activity; down regulation of cell adhesion; down-regulation of cell adhesion; downregulation of cell adhesion; inhibition of cell adhesion |
| Major function | Reduces or prevents cell adhesion, impacting cell migration, immune responses, and tissue remodeling |
| Related processes | Regulation of Rho GTPase activity, STAT1 signaling, and mechanotransduction |
| Key regulators | CD43, OLA1, CD151, EpCAM, RhoA, STAT1 |
| Disease relevance | Cancer metastasis, immune disorders, developmental abnormalities |
What Is GO:0007162?
According to QuickGO, GO:0007162 is defined as any process that stops, prevents, or reduces the frequency, rate, or extent of cell adhesion. It includes mechanisms such as inhibition of adhesion receptor activity, downregulation of adhesion molecules, and signaling events that weaken cell-cell or cell-matrix contacts.
Why Is negative regulation of cell adhesion Important in Cell Biology?
Negative regulation of cell adhesion is essential for normal physiology, enabling cells to detach during migration, immune surveillance, and tissue repair. Its dysregulation is linked to cancer metastasis, where reduced adhesion allows tumor cells to invade and spread. It also plays roles in immune cell activation and inflammation. Understanding this process provides insights into disease mechanisms and potential therapeutic strategies.
• Controls cell migration and invasion, critical for embryonic development and wound healing.
• Regulates immune cell adhesion and activation, impacting inflammatory responses.
• Involved in cancer metastasis by promoting detachment of tumor cells.
• Modulates signaling pathways such as Rho GTPase and STAT1.
• Affects cell density-dependent behaviors and tissue homeostasis.
• Provides targets for therapeutic intervention in cancer and immune diseases.
• Helps understand mechanotransduction and adhesion dynamics.
• Key for epithelial-mesenchymal transition and cell plasticity.
What Happens During negative regulation of cell adhesion?
Initiation by Adhesion Receptor Inhibition
In simple terms: The process often starts when adhesion receptors are blocked or removed from the cell surface.
Negative regulation of cell adhesion can begin with the inhibition or downregulation of adhesion receptors such as integrins or cadherins. For example, CD43 acts as a negative regulator of T-cell adhesion by interfering with receptor function. Similarly, OLA1 regulates cell-matrix adhesion by modulating focal adhesion dynamics.
Signaling Pathways That Weaken Adhesion
In simple terms: Inside the cell, signaling molecules like Rho GTPases and STAT1 transmit signals that reduce adhesion.
Rho family GTPases are key regulators of adhesion; their activity can be modulated by cell-cell and cell-matrix adhesion, leading to changes in adhesion strength. RhoA activity is also regulated by adhesion molecules and mechanotransduction, which can negatively impact adhesion. Additionally, cell adhesion and cell density can trigger STAT1 dephosphorylation, negatively regulating interferon-γ/STAT1 signaling and influencing adhesion.
Cytoskeletal Rearrangements
In simple terms: The cell's internal skeleton is reorganized to break attachments.
Cytoskeletal changes, such as actin remodeling, are often downstream of negative adhesion signals. Rho GTPases control actin dynamics, and their regulation by adhesion can lead to reduced focal adhesions and cell detachment.
Modulation by Hypoxia and Tumor Microenvironment
In simple terms: Conditions like low oxygen can alter adhesion regulation.
In colorectal cancer, hypoxia regulates CD151, which controls cell adhesion and metastasis, demonstrating environmental influence on negative regulation of adhesion.
Integration with Cell Migration and Invasion
In simple terms: Reduced adhesion allows cells to move and invade.
Negative regulation of cell adhesion is coupled with epithelial migration; for instance, EpCAM requires its Claudin-7 interaction domain to regulate epithelial migration, highlighting the interplay between adhesion and motility.
Key Genes Involved in GO:0007162 negative regulation of cell adhesion
The following genes and proteins are experimentally implicated in negative regulation of cell adhesion, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CD43 | Inhibits T-cell adhesion and activation | Immune regulation, T-cell signaling |
| OLA1 | Regulates cell-matrix adhesion | Focal adhesion dynamics, cancer |
| CD151 | Modulates cell adhesion and metastasis | Colorectal cancer, hypoxia response |
| EpCAM | Regulates epithelial migration via Claudin-7 | Epithelial-mesenchymal transition, cancer |
| RhoA | Controls actin cytoskeleton and adhesion | Mechanotransduction, cell migration |
| Rac1 | Regulates adhesion turnover | Cell motility, invasion |
| Cdc42 | Modulates filopodia and adhesion | Cell polarity, migration |
| STAT1 | Negatively regulated by adhesion | Interferon signaling, immune response |
| Claudin-7 | Interacts with EpCAM | Epithelial adhesion, cancer |
| Integrins | Adhesion receptors | Cell-matrix adhesion, signaling |
| Cadherins | Cell-cell adhesion | Tissue architecture, development |
| FAK | Focal adhesion kinase | Adhesion signaling, cancer |
| Paxillin | Focal adhesion component | Adhesion dynamics |
| Talin | Links integrins to actin | Adhesion strength |
| Kindlin | Integrin activation | Adhesion regulation |
| Vimentin | Cytoskeletal intermediate filament | Cell migration, EMT |
| Fibronectin | Extracellular matrix protein | Cell-matrix adhesion |
How Is negative regulation of cell adhesion Regulated?
Negative regulation of cell adhesion is itself regulated by various signaling pathways. Rho GTPase activity is modulated by cell-cell and cell-matrix adhesion, creating feedback loops. RhoA activity is controlled by adhesion molecules and mechanotransduction. Additionally, cell adhesion and cell density can induce STAT1 dephosphorylation, negatively regulating interferon-γ/STAT1 signaling. Hypoxia can regulate CD151, affecting adhesion in cancer.
negative regulation of cell adhesion and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CD151 | Colorectal cancer metastasis | Knockout in HCT116 cells |
| EpCAM | Epithelial cancer, migration defects | Point mutation in Claudin-7 binding domain |
| CD43 | Immune disorders, T-cell activation | Knockout in Jurkat cells |
| OLA1 | Cancer, adhesion defects | Overexpression in HeLa cells |
| STAT1 | Interferon-related diseases | Knockout in fibroblasts |
Cancer Metastasis
Negative regulation of cell adhesion is critical for cancer metastasis. Reduced adhesion allows tumor cells to detach from the primary site and invade. CD151 regulation by hypoxia controls cell adhesion and metastasis in colorectal cancer. In triple-negative breast cancer, cell adhesion-related hub genes have been identified, suggesting roles in tumor progression.
Immune Disorders
CD43 negatively regulates T-cell adhesion and activation, impacting immune responses. Dysregulation can lead to autoimmune or inflammatory conditions. STAT1 dephosphorylation via adhesion also affects interferon signaling, linking adhesion to immune regulation.
Developmental and Epithelial Disorders
EpCAM regulates epithelial migration through Claudin-7, and its dysfunction may contribute to developmental defects and cancer. Proper negative regulation of adhesion is essential for tissue morphogenesis.
From negative regulation of cell adhesion-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X negatively regulate adhesion? | CRISPR knockout in cell line (e.g., HeLa) |
| How does point mutation affect adhesion? | CRISPR point mutation (e.g., EpCAM Claudin-7 domain) |
| What is the effect of overexpression? | CRISPR knock-in of tagged gene (e.g., OLA1) |
| Which genes are involved in cancer adhesion? | CRISPR library screening in TNBC cells |
| How does hypoxia regulate adhesion? | Knockout of CD151 under hypoxia |
| What signaling pathways are affected? | Phosphoproteomics after knockout |
How to Study the negative regulation of cell adhesion Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Gene function loss | Identify negative regulators of adhesion |
| CRISPR point mutation | Specific amino acid changes | Dissect domain functions (e.g., EpCAM) |
| CRISPR knock-in | Tagged protein expression | Track localization and interactions |
| Overexpression | Gain-of-function | Study adhesion inhibition |
| Phosphoproteomics | Phosphorylation changes | Map signaling pathways |
| Live-cell imaging | Adhesion dynamics | Visualize detachment |
| RNA-seq | Transcriptional changes | Identify gene networks |
CRISPR Knockout Screening
Genome-wide CRISPR knockout screens can identify genes that negatively regulate cell adhesion. For example, screens in triple-negative breast cancer cells have highlighted adhesion-related hub genes.
Phosphoproteomics and Signaling Analysis
Phosphoproteomics can reveal changes in signaling pathways such as STAT1 dephosphorylation upon adhesion modulation. This helps map the molecular mechanisms.
Imaging and Adhesion Assays
Live-cell imaging and adhesion assays (e.g., detachment assays) quantify changes in adhesion strength after genetic manipulation.
Transcriptomics and Bioinformatics
RNA-seq and bioinformatics analyses identify differentially expressed genes and pathways related to negative regulation of adhesion, as shown in breast cancer studies.
How CRISPR Can Be Used to Study GO:0007162 negative regulation of cell adhesion
Knockout
CRISPR knockout is used to delete genes like CD151 or OLA1 to assess their role in negative regulation of adhesion. For instance, knockout of CD151 in colorectal cancer cells can reduce metastasis.
Point Mutation
Point mutations can be introduced to disrupt specific interactions, such as the Claudin-7 binding domain of EpCAM, to study its role in epithelial migration.
Knock-in
Knock-in of tagged versions of genes (e.g., GFP-OLA1) allows visualization and functional analysis of adhesion regulation.
Overexpression
Overexpression of negative regulators like CD43 can inhibit T-cell adhesion, providing insights into immune regulation.
How EDITGENE Supports negative regulation of cell adhesion Research
Researchers studying negative regulation of cell adhesion-related genes often need to determine whether a candidate gene is causally involved in adhesion control. EDITGENE provides CRISPR-based services to create precise cell models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of cell adhesion research.
Frequently Asked Questions About negative regulation of cell adhesion
What is negative regulation of cell adhesion (GO:0007162)?
It is any process that stops, prevents, or reduces the frequency, rate, or extent of cell adhesion, as defined by QuickGO.
What genes are involved in negative regulation of cell adhesion?
Key genes include CD43, OLA1, CD151, EpCAM, RhoA, and STAT1, among others.
How does negative regulation of cell adhesion affect cancer?
It promotes metastasis by allowing tumor cells to detach and invade; CD151 and EpCAM are examples.
What are the synonyms for GO:0007162?
Synonyms include cell adhesion receptor inhibitor activity, down regulation of cell adhesion, and inhibition of cell adhesion.
Which diseases are linked to negative regulation of cell adhesion?
Cancer metastasis, immune disorders, and developmental defects.
What methods study negative regulation of cell adhesion?
CRISPR knockout, point mutation, knock-in, overexpression, phosphoproteomics, and imaging.
How is RhoA involved in negative regulation of cell adhesion?
RhoA activity is regulated by adhesion molecules and mechanotransduction, influencing adhesion strength.
What is the role of CD43 in adhesion?
CD43 negatively regulates T-cell adhesion and activation.
Can CRISPR screens identify adhesion regulators?
Yes, genome-wide screens have identified hub genes in triple-negative breast cancer.
What cell models are used to study negative regulation of cell adhesion?
Common models include HeLa, HCT116, Jurkat, and breast cancer cell lines with CRISPR modifications.
Conclusion
Negative regulation of cell adhesion (GO:0007162) is a vital biological process that controls cell detachment, migration, and signaling. Its dysregulation underlies cancer metastasis and immune disorders. By leveraging CRISPR-based models and omics approaches, researchers can dissect the molecular players and pathways, paving the way for targeted therapies. EDITGENE offers comprehensive services to support such studies.
References
- 1. Jeyabal PV et al.. 2014. Regulation of cell-matrix adhesion by OLA1, the Obg-like ATPase 1.. Biochem Biophys Res Commun 444(4):568-74 PMID: 24486488
- 2. Manjunath N et al.. 1995. Negative regulation of T-cell adhesion and activation by CD43.. Nature 377(6549):535-8 PMID: 7566153
- 3. Barth AIM et al.. 2018. Regulation of epithelial migration by epithelial cell adhesion molecule requires its Claudin-7 interaction domain.. PLoS One 13(10):e0204957 PMID: 30304739
- 4. Arthur WT et al.. 2002. Regulation of Rho family GTPases by cell-cell and cell-matrix adhesion.. Biol Res 35(2):239-46 PMID: 12415742
- 5. Marjoram RJ et al.. 2014. Regulation of RhoA activity by adhesion molecules and mechanotransduction.. Curr Mol Med 14(2):199-208 PMID: 24467208
- 6. Chen Z et al.. 2011. Negative regulation of interferon-γ/STAT1 signaling through cell adhesion and cell density-dependent STAT1 dephosphorylation.. Cell Signal 23(8):1404-12 PMID: 21511030
- 7. Chien CW et al.. 2008. Regulation of CD151 by hypoxia controls cell adhesion and metastasis in colorectal cancer.. Clin Cancer Res 14(24):8043-51 PMID: 19073968
- 8. Han YH et al.. 2023. Identification of Hub Genes and Upstream Regulatory Factors Based on Cell Adhesion in Triple-negative Breast Cancer by Integrated Bioinformatical Analysis.. Anticancer Res 43(7):2951-2964 PMID: 37351977
