Focal Adhesion Signaling in Cell Migration

Cell migration is orchestrated by dynamic interactions between the intracellular cytoskeleton and the extracellular matrix via specialised multi‐protein assemblies known as focal adhesions. These structures serve both as mechanical anchors and signalling hubs, coordinating the spatial and temporal activation of kinases and adaptor proteins that regulate protrusion, adhesion turnover and contractility. Central to this process is focal adhesion kinase (FAK), a non‐receptor tyrosine kinase recruited and activated by integrin engagement. Upon ligand binding, integrins cluster and recruit FAK, which undergoes autophosphorylation and scaffolds downstream effectors such as Src family kinases, paxillin and p130Cas. This cascade modulates actin polymerisation and myosin activity, driving lamellipodial extension and traction force generation. The balance between adhesion assembly at the leading edge and disassembly at the rear dictates migration speed and directionality, with dysregulation implicated in developmental defects, impaired wound healing and metastatic invasion. Emerging insights reveal that mechanical properties of the microenvironment and biochemical signals converge on focal adhesion components, fine‐tuning cell motility in physiological and pathological contexts.

Research from Nature Portfolio

A seminal investigation demonstrated that FAK is directly recruited by β1 integrin and that its kinase activity is essential for fibroblasts to traverse fibronectin matrices. Selective inhibition of FAK attenuated downstream signalling cascades, reduced focal adhesion turnover and mitigated fibrosis in murine models. This work highlights the therapeutic potential of targeting FAK‐mediated adhesion signalling to control aberrant cell migration in fibrotic diseases.

Focal Adhesion Signaling in Cell Migration publication trend

The graph below shows the total number of articles in focal adhesion signaling in cell migration across all publications each year (not limited to Nature Index journals).

Technical terms

Focal adhesion: A specialised multi‐protein complex that links the extracellular matrix to the actin cytoskeleton and transduces mechanical and biochemical signals.

Integrin: A transmembrane receptor that binds extracellular matrix ligands and initiates intracellular signalling cascades.

Focal Adhesion Kinase (FAK): A cytoplasmic non‐receptor tyrosine kinase activated by integrin clustering, central to adhesion turnover and cell migration.

Extracellular matrix: The network of proteins and polysaccharides outside cells that provides structural support and signalling cues.

Autophosphorylation: The process by which a kinase phosphorylates itself on specific tyrosine residues, regulating its activation state.

References

1. Bacopa monnieri phytochemicals regulate fibroblast cell migration via modulation of focal adhesions. iScience (2024).
2. Focal Adhesion Kinase Regulates Fibroblast Migration via Integrin beta-1 and Plays a Central Role in Fibrosis. Scientific Reports (2016).
3. FAK-Dependent Cell Motility and Cell Elongation. Cells (2020).
4. Integrin-mediated cell adhesion activates mitogen-activated protein kinases.. Journal of Biological Chemistry (1994).
5. Phosphorylation of Tyrosine 397 in Focal Adhesion Kinase Is Required for Binding Phosphatidylinositol 3-Kinase*. Journal of Biological Chemistry (1996).
6. Characterization of Tyrosine Phosphorylation of Paxillin in Vitro by Focal Adhesion Kinase *. Journal of Biological Chemistry (1995).
7. p130Cas, a Substrate Associated with v-Src and v-Crk, Localizes to Focal Adhesions and Binds to Focal Adhesion Kinase*. Journal of Biological Chemistry (1996).
8. Focal Adhesion Kinase Overexpression Enhances Ras-dependent Integrin Signaling to ERK2/Mitogen-activated Protein Kinase through Interactions with and Activation of c-Src*. Journal of Biological Chemistry (1997).