negative regulation of cell-substrate adhesion

Definition

Target type: biologicalprocess

Any process that decreases the frequency, rate or extent of cell-substrate adhesion. Cell-substrate adhesion is the attachment of a cell to the underlying substrate via adhesion molecules. [GOC:dph, GOC:pf, GOC:tb]

Negative regulation of cell-substrate adhesion is a crucial process that governs cell migration, tissue morphogenesis, and wound healing. It involves the downregulation of adhesion molecules, such as integrins, cadherins, and selectins, which mediate the attachment of cells to the extracellular matrix (ECM) or other cells. This complex process is tightly regulated by a variety of signaling pathways, including intracellular signaling cascades, extracellular matrix components, and mechanical cues. Key mechanisms involved in negative regulation of cell-substrate adhesion include:
1. **Ligand-mediated signaling:** Binding of specific ligands to adhesion molecules can trigger intracellular signaling cascades that lead to the detachment of cells from the substrate. For instance, binding of soluble factors like cytokines or chemokines to integrins can induce phosphorylation of intracellular signaling proteins, leading to the disassembly of focal adhesions, which are specialized structures that connect integrins to the cytoskeleton.
2. **Proteolytic cleavage of adhesion molecules:** Enzymes such as matrix metalloproteinases (MMPs) and ADAMs (a disintegrin and metalloprotease) can cleave adhesion molecules, disrupting their ability to bind to their ligands and leading to cell detachment.
3. **Cytoskeleton remodeling:** The cytoskeleton, which provides structural support to cells, plays a crucial role in cell-substrate adhesion. Modifications to the cytoskeleton, such as depolymerization of actin filaments or microtubule disassembly, can weaken cell adhesion.
4. **Changes in intracellular signaling pathways:** Several intracellular signaling pathways, such as the Rho GTPase pathway, the PI3K/Akt pathway, and the MAPK pathway, are involved in regulating cell-substrate adhesion. Activation or inhibition of these pathways can modulate the expression, activity, and localization of adhesion molecules, ultimately affecting cell adhesion.
5. **Mechanical cues:** External forces, such as shear stress or tension, can influence cell-substrate adhesion. Cells can respond to these cues by altering the expression and activity of adhesion molecules and their associated signaling pathways, leading to changes in cell adhesion.
6. **Regulation of gene expression:** Transcription factors and other regulatory elements can control the expression of genes encoding adhesion molecules, influencing the amount of these molecules available for cell-substrate interaction.
Overall, negative regulation of cell-substrate adhesion is a dynamic and multifaceted process that involves a complex interplay of molecular mechanisms. Its proper regulation is essential for maintaining tissue homeostasis, facilitating cell migration during development and wound healing, and preventing uncontrolled cell adhesion that can lead to pathological conditions such as tumor metastasis.'
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Proteins (3)

Compounds (43)