Integrin-Mediated Mechanisms in Cancer Biology

Integrins are transmembrane receptors that mediate the adhesion between cells and the extracellular matrix (ECM), translating mechanical and chemical signals into intracellular responses. In cancer, dysregulated integrin expression and activation promote malignant hallmarks including unchecked proliferation, resistance to apoptosis, enhanced migration and invasion, and metastatic dissemination. Specific integrin heterodimers such as αvβ3, αvβ6 and α5β1 interact with ECM ligands—fibronectin, vitronectin and tenascin—to remodel the tumour microenvironment, activate latent growth factors like transforming growth factor-β (TGF-β) and orchestrate cytoskeletal dynamics via Rho-family GTPases. Beyond direct tumour-cell effects, integrin signalling modulates angiogenesis, immune cell recruitment and stromal fibrosis. The bidirectional nature of integrin engagement, whereby intracellular tension and ECM stiffness reciprocally reinforce one another, underpins mechanotransduction pathways that drive aggressive phenotypes. Integrins have thus emerged as versatile biomarkers for diagnostics and as targets for antibody-, peptide- and small-molecule-based therapies and imaging agents, with several strategies now advancing through preclinical and early clinical stages.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Integrin-Mediated Mechanisms in Cancer Biology publication trend

The graph below shows the total number of articles in integrin-mediated mechanisms in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Integrin: A heterodimeric transmembrane receptor that binds ECM proteins and links them to the actin cytoskeleton to regulate cell adhesion and signalling.

Extracellular matrix (ECM): The complex network of proteins and polysaccharides surrounding cells, providing structural support and biochemical cues.

Mechanotransduction: The process by which cells convert mechanical stimuli from the ECM into biochemical signals that influence behaviour and fate.

Tumour microenvironment (TME): The local cellular and non-cellular milieu of a tumour, including stromal cells, immune infiltrates, ECM and soluble factors.

Peptide-drug conjugate (PDC): A targeted therapeutic where a cytotoxic agent is linked to a peptide ligand that binds selectively to a cell-surface receptor such as an integrin.

References

1. Extracellular matrix and its therapeutic potential for cancer treatment. Signal Transduction and Targeted Therapy (2021).
2. PET/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the “Cancer Integrin” αvβ6 with Ga-68-Trivehexin. European Journal of Nuclear Medicine and Molecular Imaging (2021).
3. Integrin αvβ6-specific therapy for pancreatic cancer developed from foot-and-mouth-disease virus. Theranostics (2020).
4. Pro‐migratory and TGF‐β‐activating functions of αvβ6 integrin in pancreatic cancer are differentially regulated via an Eps8‐dependent GTPase switch. The Journal of Pathology (2017).