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Integrin and Its Associated Proteins As a Mediator for Mechano-Signal Transduction

Overview
Journal Biomolecules
Publisher MDPI
Date 2025 Feb 26
PMID 40001469
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Abstract

Mechano-signal transduction is a process in which cells perceive extracellular mechanical signals, convert them into intracellular biochemical signals, and produce a response. Integrins are cell surface receptors that sense the extracellular mechanical cues and bind to the extracellular matrix (ECM). This binding induces integrin clustering and activation. Cytoplasmic tails of activated integrins interact and induce cytoskeleton tensions via several adaptor proteins. Integrins monitor extracellular stiffness via cytoskeleton tensions and modulate ECM stiffness via downstream signaling pathways regulating the expression of genes of ECM components. Integrin-mediated mechano-transduction is very crucial for the cell as it regulates the cell physiology both in normal and diseased conditions according to extracellular mechanical cues. It regulates cell proliferation, survival, and migration. Abnormal mechanical cues such as extreme and prolonged mechanical stress result in pathological conditions including fibrosis, cancers, skin, and autoimmune disorders. This paper aims to explore the role of integrins and their associated proteins in mechano-signal transduction. It highlights the integrins and their associated proteins as targets for therapy development. Furthermore, it also presents the challenges to the targeted drug development, which can be drug resistance and cytotoxicity. It is concluded in this paper that research on integrin-mediated mechano-signal transduction and its relationship with cell physiology and pathologies will be an important step towards the development of effective therapies.

References
1.
Guilluy C, Swaminathan V, Garcia-Mata R, OBrien E, Superfine R, Burridge K . The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins. Nat Cell Biol. 2011; 13(6):722-7. PMC: 3107386. DOI: 10.1038/ncb2254. View

2.
Sen M, Yuki K, Springer T . An internal ligand-bound, metastable state of a leukocyte integrin, αXβ2. J Cell Biol. 2014; 203(4):629-42. PMC: 3840939. DOI: 10.1083/jcb.201308083. View

3.
Takagi J, Petre B, Walz T, Springer T . Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell. 2002; 110(5):599-11. DOI: 10.1016/s0092-8674(02)00935-2. View

4.
Auernheimer V, Lautscham L, Leidenberger M, Friedrich O, Kappes B, Fabry B . Vinculin phosphorylation at residues Y100 and Y1065 is required for cellular force transmission. J Cell Sci. 2015; 128(18):3435-43. PMC: 4582403. DOI: 10.1242/jcs.172031. View

5.
Mierke C . Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells. Cells. 2024; 13(1). PMC: 10777970. DOI: 10.3390/cells13010096. View