Integrin Signaling in Epithelial Cell Function and Cancer
Summary
Integrins are heterodimeric transmembrane receptors that mediate bidirectional communication between the extracellular matrix and intracellular signalling networks. In epithelia, they coordinate adhesion, migration, proliferation and survival through assembly of focal adhesions, recruitment of kinases such as focal adhesion kinase (FAK) and modulation of downstream cascades including the PI3K–Akt and RAS–ERK pathways. Dysregulated integrin expression or function alters epithelial architecture and promotes tumour initiation, invasion and metastasis. Variations in integrin subunit composition, receptor clustering and crosstalk with growth factor receptors enable dynamic control of cell behaviour in normal tissue homeostasis and during malignant transformation. The emerging picture highlights integrins as mechanosensors and signalling hubs that influence cytoskeletal dynamics, gene expression programmes and resistance to programmed cell death (anoikis). These properties underpin their role in cancer cell dissemination and suggest avenues for therapeutic intervention aimed at restoring normal adhesion signalling or selectively targeting pathogenic integrin complexes.
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Integrin Signaling in Epithelial Cell Function and Cancer publication trend
The graph below shows the total number of articles in integrin signaling in epithelial cell function and cancer 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 extracellular matrix ligands and transmits signals bidirectionally across the cell membrane.
Focal adhesion kinase (FAK): A cytoplasmic tyrosine kinase recruited to integrin clusters that phosphorylates downstream targets to regulate adhesion, motility and survival.
Anoikis: Programmed cell death induced by detachment from the extracellular matrix, preventing inappropriate cell survival and metastasis.
Hemidesmosome: A specialised adhesion complex that anchors epithelial cells to the basement membrane via integrin α6β4 and associated proteins.
Extracellular matrix (ECM): A network of proteins and polysaccharides secreted by cells that provides structural support and biochemical cues for tissue integrity and cell signalling.
References
- Integrin α6β4 in Colorectal Cancer: Expression, Regulation, Functional Alterations and Use as a Biomarker. Cancers (2019).
- Roles of Integrins in Gastrointestinal Cancer Metastasis. Frontiers in Molecular Biosciences (2021).
- Integrin α1 promotes tumorigenicity and progressive capacity of colorectal cancer. International Journal of Biological Sciences (2020).
- Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinal epithelial crypt cells: selective engagement and roles of PI3-K isoform complexes. Apoptosis (2012).
- Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity. BMC Cancer (2009).
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