The role and regulation of integrins in cell migration and invasion

: Chastney, Megan R.; Kaivola, Jasmin; Leppänen, Veli-Matti; Ivaska, Johanna

Publisher: Springer Science and Business Media LLC

: 2025

: Nature Reviews Molecular Cell Biology

: Nat Rev Mol Cell Biol

: 26

: 2

: 147

: 167

: 1471-0072

: 1471-0080

DOI: https://doi.org/10.1038/s41580-024-00777-1(external)

: http://dx.doi.org/10.1038/s41580-024-00777-1(external)

Integrin receptors are the main molecular link between cells and the extracellular matrix (ECM) as well as mediating cell-cell interactions. Integrin-ECM binding triggers the formation of heterogeneous multi-protein assemblies termed integrin adhesion complexes (IACs) that enable integrins to transform extracellular cues into intracellular signals that affect many cellular processes, especially cell motility. Cell migration is essential for diverse physiological and pathological processes and is dysregulated in cancer to favour cell invasion and metastasis. Here, we discuss recent findings on the role of integrins in cell migration with a focus on cancer cell dissemination. We review how integrins regulate the spatial distribution and dynamics of different IACs, covering classical focal adhesions, emerging adhesion types and adhesion regulation. We discuss the diverse roles integrins have during cancer progression from cell migration across varied ECM landscapes to breaching barriers such as the basement membrane, and eventual colonization of distant organs.

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This work was supported by the Finnish Cancer Institute (K. Albin Johansson Professorship, to J.I.); a Research Council of Finland Centre of Excellence programme, Biological Barrier Mechanics and Disease (346131 and 364182, to J.I.); the Cancer Foundation Finland (to J.I.); the Sigrid Juselius Foundation (to J.I.); the Research Council of Finland’s Flagship InFLAMES (337530 and 357910); the Jane and Aatos Erkko Foundation (to J.I.); a Research Council of Finland postdoctoral research grant (343239, to M.R.C.); the Turku Doctoral Programme of Molecular Medicine (TuDMM) (to J.K.); and the Finnish Cultural Foundation (to J.K.).