Integrin-Mediated Cell Adhesion in Cancer Progression

Integrins are transmembrane receptors composed of non-covalently associated α and β subunits that mediate bidirectional signalling between cells and the extracellular matrix. Through specific recognition of matrix ligands such as fibronectin, vitronectin and collagen, integrins organise focal adhesions that link the cytoskeleton to the tumour microenvironment and activate intracellular kinases including focal adhesion kinase and Src. These signalling hubs regulate cell survival, proliferation, motility and invasion, and are co-opted by malignant cells to drive angiogenesis, intravasation and metastatic colonisation. Dynamic regulation of integrin expression and affinity, together with crosstalk with growth factor receptors and mechanotransduction pathways, shapes the invasive behaviour and therapy resistance of tumours. Understanding the structural basis of integrin heterodimerisation, ligand recognition motifs and downstream adhesion complexes is therefore central to the development of new anti-cancer strategies.

Research from Nature Portfolio

Recent studies have harnessed high-resolution CRISPR screening to map the functional landscape of cell surface receptors in multiple cancer models. These efforts pinpointed the integrin αVβ5 heterodimer as essential for tumour cell expansion and identified a central β-propeller pocket within the αV subunit that governs heterodimer stability. A computer-aided CRISPR-tiling pipeline guided the development of a lead small-molecule inhibitor, Cpd_AV2, which rapidly disrupts αVβ5 assembly and induces apoptosis in tumour cells. In parallel, a systematic evaluation of RGD-binding integrin ligands using standardised binding assays has provided a comprehensive profile of affinity and selectivity across multiple αV and β1-series receptors, informing the choice of peptidic or peptidomimetic candidates for targeted imaging and therapy.

Integrin-Mediated Cell Adhesion in Cancer Progression publication trend

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

Technical terms

Integrin: A heterodimeric transmembrane receptor that binds extracellular matrix ligands and transduces signals to the cytoskeleton.

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

Focal adhesion: A multi-protein complex linking integrins to actin filaments and coordinating cell adhesion and signalling.

RGD motif: A conserved sequential triad of arginine–glycine–aspartate in ECM proteins recognised by specific integrins.

CRISPR screening: A gene editing approach that uses guide RNAs to systematically probe the function of multiple genomic loci.

References

1. A novel class of inhibitors that disrupts the stability of integrin heterodimers identified by CRISPR-tiling-instructed genetic screens. Nature Structural & Molecular Biology (2024).
2. A Comprehensive Evaluation of the Activity and Selectivity Profile of Ligands for RGD-binding Integrins. Scientific Reports (2017).
3. ID4-dependent secretion of VEGFA enhances the invasion capability of breast cancer cells and activates YAP/TAZ via integrin β3-VEGFR2 interaction. Cell Death & Disease (2024).
4. L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma. Cell Death Discovery (2023).