Integrin Adhesion Receptors in Health and Disease

Integrin adhesion complexes (IACs) are the main components involved in cell adhesion to the extracellular matrix (ECM) and serve as key sensors of signals coming from the microenvironment. IAC adhesions are mediated by the integrin protein family enabling binding to various ligands of the ECM and counter receptors on neighbouring cells. Cells sense the chemical and mechanical properties of their environment through integrins clustered in punctuate IACs known as cell-matrix adhesions that are connected to the actin cytoskeleton, microtubules and intermediate filaments. One key property of IACs that is essential for tissue homeostasis is their role as sites of mechanotransduction, a process whereby cells are able to sense and respond to mechanical cues and convert them into biological signals to elicit different cellular responses. The dense, highly dynamic protein complex associated with IACs is referred to as the adhesome and its mis-regulation is central to a wide variety of developmental and pathological processes.

Despite their incredible diversity in different cell types, IACs have much in common, including shared cytoskeletal linkages, the ability to recruit diverse signalling molecules and adaptor proteins in a context dependent manner, so as to enable the regulation of multiple cellular functions like cell polarity, cell migration, proliferation and survival, differentiation and morphogenesis. The mechanotransduction processes at adhesion sites occur across different scales both within the cell and within tissues. In the last 10 years, the field of integrin-mediated mechanotransduction has exploded, as the role of mechanotransduction in driving cell fate has become apparent. A cell responds to its outside environment, e.g. the stiffness or deformation of the extracellular environment, which is sensed through increased tension at IACs. This sensing in turn alters transcriptional programs that control proliferation, cellular stemness, and lineage differentiation. Out of the core 60-protein consensus integrin adhesome, 32 have been shown to be involved in cancer development and progression. From the 232 integrin adhesome genes queried within the OMIM database, 52 (22%) were linked to specific genetic disease which represents an enrichment of disease-causing genes in the adhesome compared with the genomic population that is 11%. As integrins are expressed and accessible at the cell surface, integrin-targeting drugs have a great potential to be used in the clinic.

This Research Topic aims at bringing together contributions regarding basic biology of IAC components and contributions concerning identification of candidate therapeutic strategies for clinical translation. Theoretical or computation models are also preferred. In this Research Topic authors are welcome to submit original articles, mini-reviews, or reviews considering following subtopics:

- Biological and physiological significance of integrins

- Integrin adhesion complexes: composition and mechanotransduction

- Molecular basis of signaling to and from integrins

- Integrins in cell polarity, migration, proliferation, survival, differentiation and morphogenesis

- Integrins and extracellular matrix

- Integrins as therapeutic targets

- Theoretical or computational models of integrins at molecular, cellular or tissue scales