Integrin Signaling in Cancer Progression and Metastasis

Integrins are heterodimeric transmembrane receptors that mediate adhesion between cells and the extracellular matrix, orchestrating bidirectional signalling that governs cancer cell behaviour. In the initial stages of tumourigenesis, altered integrin expression can facilitate aberrant proliferation and survival by cooperating with growth factor receptors and activating downstream effectors such as focal adhesion kinase (FAK) and Src family kinases. As tumours evolve, mechanotransduction through integrins senses changes in matrix stiffness, promoting focal adhesion assembly and cytoskeletal reorganisation that underpin cell motility and invasion. The epithelial-to-mesenchymal transition (EMT), a key precursor to metastasis, is often driven by integrin-dependent activation of pathways including PI3K/Akt, MAPK/Erk and TGFβ. Once disseminated, circulating tumour cells exploit specific integrin subtypes, notably β1 and α5β1, to adhere to endothelium and extravasate into distant organs. Integrin signalling also modulates immune cell recruitment and angiogenesis within the tumour microenvironment, further enhancing metastatic colonisation. Emerging insights into the molecular crosstalk between integrins and chemokine networks have highlighted new vulnerabilities, suggesting that targeted modulation of integrin activation or downstream transcriptional programmes could impede both local invasion and systemic spread.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Integrin Signaling in Cancer Progression and Metastasis publication trend

The graph below shows the total number of articles in integrin signaling in cancer progression and metastasis across all publications each year (not limited to Nature Index journals).

Technical terms

Integrin: A transmembrane αβ heterodimer that connects the extracellular matrix to the cytoskeleton and transmits bidirectional signals.

Inside-out signalling: Intracellular pathways that increase integrin affinity for ligands by inducing conformational changes in the extracellular domain.

Outside-in signalling: Extracellular ligand binding to integrins that triggers intracellular kinase activation, cytoskeletal reorganisation and gene expression changes.

Focal adhesion kinase (FAK): A non-receptor tyrosine kinase recruited to activated integrins, central to cell migration and survival pathways.

Epithelial-to-mesenchymal transition (EMT): A process by which epithelial cells acquire mesenchymal traits, enhancing motility and invasiveness.

MRTF/SRF: A transcriptional complex activated downstream of actin dynamics that regulates expression of genes involved in adhesion and motility.

References

1. Tumor cell integrin β4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo. Journal of Hematology & Oncology (2023).
2. The interaction of β-arrestin1 with talin1 driven by endothelin A receptor as a feature of α5β1 integrin activation in high-grade serous ovarian cancer. Cell Death & Disease (2023).
3. Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities. Cell Communication and Signaling (2023).
4. IQGAP1 and NWASP promote human cancer cell dissemination and metastasis by regulating β1-integrin via FAK and MRTF/SRF. Cell Reports (2024).
5. Mechanotransduction of matrix stiffness in regulation of focal adhesion size and number: reciprocal regulation of caveolin-1 and β1 integrin. Scientific Reports (2017).