Focal Adhesion Kinase Signaling in Cancer Biology

Focal adhesion kinase (FAK) is a central regulator of how cells sense and respond to their surroundings. Situated at integrin-based adhesions, FAK transmits signals from the extracellular matrix and growth factors to intracellular pathways that govern cell proliferation, survival, migration and invasion. In cancer, aberrant FAK activity is widely implicated in tumour progression, metastasis and therapy resistance. By scaffolding key adaptor proteins and phosphorylating downstream effectors, FAK modulates cytoskeletal dynamics and influences epithelial–mesenchymal transition, facilitating dissemination of malignant cells. Beyond its canonical cytoplasmic role, FAK also translocates to the nucleus, where it interacts with transcription factors to control gene expression programmes related to cell cycle, immune evasion and chemokine secretion. Within the tumour microenvironment, FAK orchestrates cross-talk between cancer cells, stromal fibroblasts, endothelial cells and infiltrating immune cells, promoting angiogenesis, immunosuppression and extracellular matrix remodelling. These multifaceted functions render FAK an attractive therapeutic target. Small-molecule inhibitors of FAK kinase activity, employed alone or in strategic combinations with chemotherapy, targeted agents or immunotherapies, have shown promise in preclinical models. Current research focuses on unravelling context-dependent FAK signalling networks, elucidating mechanisms of resistance and optimising combination regimens to maximise clinical benefit while minimising adverse effects.

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Focal Adhesion Kinase Signaling in Cancer Biology publication trend

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

Technical terms

Focal adhesion kinase (FAK): A cytoplasmic non-receptor tyrosine kinase that transduces signals from integrins and growth factors to regulate cell adhesion, motility and survival.

Tumour microenvironment (TME): The complex milieu of cancer cells, stromal cells, extracellular matrix and immune components that influences tumour growth and therapy response.

Immunogenic cell death (ICD): A form of regulated cell death that releases signals to activate the immune system against dying cancer cells.

Ferroptosis: An iron-dependent form of cell death characterised by accumulation of lipid peroxides.

Kinase inhibitor: A small molecule designed to block the enzymatic activity of protein kinases by competing with ATP or substrate binding.

Integrin: A family of transmembrane receptors that mediate cell attachment to the extracellular matrix and initiate intracellular signalling cascades.

References

1. Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade. Journal of Experimental & Clinical Cancer Research (2024).
2. Simultaneous inhibition of FAK and ROS1 synergistically repressed triple-negative breast cancer by upregulating p53 signalling. Biomarker Research (2024).
3. LAIR1 drives glioma progression by nuclear focal adhesion kinase dependent expressions of cyclin D1 and immunosuppressive chemokines/cytokines. Cell Death & Disease (2023).