Abstract
Integrins are heterodimeric cell surface receptors composed of α and β subunits that control adhesion, proliferation and gene expression. The integrin heterodimer binding to ligand reorganises the cytoskeletal networks and triggers multiple signalling pathways that can cause changes in cell cycle, proliferation, differentiation, survival and motility. In addition, integrins have been identified as targets for many different diseases, including cancer. Integrin crosstalk is a mechanism by which a change in the expression of a certain integrin subunit or the activation of an integrin heterodimer may interfere with the expression and/or activation of other integrin subunit(s) in the very same cell. Here, we review the evidence for integrin crosstalk in a range of cellular systems, with a particular emphasis on cancer. We describe the molecular mechanisms of integrin crosstalk, the effects of cell fate determination, and the contribution of crosstalk to therapeutic outcomes. Our intention is to raise awareness of integrin crosstalk events such that the contribution of the phenomenon can be taken into account when researching the biological or pathophysiological roles of integrins.
Highlights
Integrins are a large family of ubiquitously expressed transmembrane glycoprotein receptors that function as major sensors of the extracellular environment and regulate many aspects of cell behaviour.The majority of integrins are involved in cell–extracellular-matrix (ECM) interactions, while some of them participate in cell–cell interactions
Those assembled as heterodimers, the process which occurs in the endoplasmic reticulum (ER), are displayed on the cell surface and are able to bind their ligands and trigger signalling [31]
Koivisto et al [104] showed that depletion of the pre-β1 integrin subunit pools in ER, accelerates the maturation rate of the pre-β1 integrin subunit, which slows down the maturation of the α3 and α5 subunits
Summary
Integrins are a large family of ubiquitously expressed transmembrane glycoprotein receptors that function as major sensors of the extracellular environment and regulate many aspects of cell behaviour. Different integrins bind different ECM proteins and/or cell surface molecules that have a specific spatial and temporal distribution pattern in a given tissue. Highlight the published describing integrin structure function, as well as IAC composition. These versatility of integrin family and its contribution to different aspects of cell behaviour. Reviews highlight the versatility of integrin family and its contribution to different aspects of cell the preciseConsequently, and dynamic regulation thedynamic expression of a single integrin type has potential to behaviour. Since affecting the activation/expression of another integrin and we use the umbrella term of integrin crosstalk. We emphasize the potential clinical implications of this phenomenon
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