Integrin-Mediated Cell-Extracellular Matrix Interactions in Tumor Biology

Integrins are transmembrane heterodimeric receptors that anchor cells to the extracellular matrix (ECM) and transduce signals in both directions across the plasma membrane. In tumours, integrin–ECM interactions regulate key processes such as cell proliferation, survival, migration and invasion, shaping the tumour microenvironment and influencing metastatic spread. By engaging ECM ligands such as fibronectin, laminin and collagens, integrins cluster into focal adhesions and recruit cytoplasmic kinases and adaptor proteins, thereby initiating signalling cascades—including FAK/Src, PI3K/AKT and MAPK pathways—that converge on cytoskeletal remodelling and gene expression programmes. Tumour cells often exploit altered ECM composition and stiffness to enhance integrin signalling, promoting mechanotransduction that sustains malignant phenotypes. Moreover, integrins modulate the activation and sequestration of growth factors, contribute to angiogenesis and regulate stromal cell behaviour. Dysregulated integrin expression or function is implicated in resistance to chemotherapy and radiotherapy, making integrin–ECM interactions attractive targets for therapeutic intervention. Recent advances have begun to unravel the dynamic interplay between integrins, ECM remodellers and mechanical cues within primary tumours and at metastatic niches, offering new opportunities to disrupt pathological adhesion and signalling networks.

Research from Nature Portfolio

Recent studies have elucidated how ECM components and mechanical forces interface with integrin-mediated signalling to influence tumour biology. In one investigation of mammary epithelial architecture, loss of the ECM glycoprotein fibulin-2 was shown to disrupt basement membrane integrity and downregulate integrin β1, leading to aberrant spheroid growth and enhanced invasive capacity. This work highlights the importance of tumour cell-derived matrix stabilisers in preserving integrin-dependent adhesion and preventing early invasion. In a complementary genome-wide analysis of mechanically stretched skin, sequential transcriptional changes revealed time-dependent induction of ECM-remodelling enzymes, mechanoresponsive genes and integrin-linked adhesion molecules. These findings demonstrate that sustained mechanical stimuli drive hierarchical activation of immune response, cytoskeletal reorganisation and integrin-mediated adhesion programmes, underscoring parallels between tissue expansion and the stiffened microenvironments encountered by solid tumours.

Integrin-Mediated Cell-Extracellular Matrix Interactions in Tumor Biology publication trend

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

Technical terms

Integrin: A heterodimeric transmembrane receptor composed of α and β subunits that binds ECM proteins and transduces bidirectional signals across the cell membrane.

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

Focal adhesion: A multi-protein complex where clustered integrins link the ECM to the actin cytoskeleton and recruit kinases to initiate downstream signalling.

Mechanotransduction: The process by which cells convert mechanical stimuli, such as matrix stiffness or stretch, into biochemical signals that regulate behaviour.

Metastasis: The multi-step dissemination of tumour cells from a primary site to distant organs, involving detachment, invasion, intravasation, survival in circulation, extravasation and colonisation.

References

1. Beyond adhesion: emerging roles for integrins in control of the tumor microenvironment. F1000Research (2017).
2. Fibulin-2 is required for basement membrane integrity of mammary epithelium. Scientific Reports (2018).
3. Transcriptomic analysis reveals dynamic molecular changes in skin induced by mechanical forces secondary to tissue expansion. Scientific Reports (2020).
4. ADAMTS18 deficiency associates extracellular matrix dysfunction with a higher risk of HER2-positive mammary tumorigenesis and metastasis. Breast Cancer Research (2024).
5. ITGA3–MET interaction promotes papillary thyroid cancer progression via ERK and PI3K/AKT pathways. Annals of Medicine (2025).