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Integrin
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=== Signal transduction === Integrins play an important role in cell signaling by modulating the cell signaling pathways of transmembrane protein kinases such as receptor tyrosine kinases (RTK). While the interaction between integrin and receptor tyrosine kinases originally was thought of as uni-directional and supportive, recent studies indicate that integrins have additional, multi-faceted roles in cell signaling. Integrins can regulate the receptor tyrosine kinase signaling by recruiting specific adaptors to the plasma membrane. For example, Ξ²1c integrin recruits Gab1/Shp2 and presents Shp2 to IGF1R, resulting in dephosphorylation of the receptor.<ref>{{cite journal | vauthors = Goel HL, Breen M, Zhang J, Das I, Aznavoorian-Cheshire S, Greenberg NM, Elgavish A, Languino LR | title = beta1A integrin expression is required for type 1 insulin-like growth factor receptor mitogenic and transforming activities and localization to focal contacts | journal = Cancer Research | volume = 65 | issue = 15 | pages = 6692β700 | date = August 2005 | pmid = 16061650 | doi = 10.1158/0008-5472.CAN-04-4315 | doi-access = }}</ref> In a reverse direction, when a receptor tyrosine kinase is activated, integrins co-localise at focal adhesion with the receptor tyrosine kinases and their associated signaling molecules. The repertoire of integrins expressed on a particular cell can specify the signaling pathway due to the differential binding affinity of ECM ligands for the integrins. The tissue stiffness and matrix composition can initiate specific signaling pathways regulating cell behavior. Clustering and activation of the integrins/actin complexes strengthen the focal adhesion interaction and initiate the framework for cell signaling through assembly of adhesomes.<ref name="pmid21307119">{{cite journal | vauthors = Kim SH, Turnbull J, Guimond S | title = Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor | journal = The Journal of Endocrinology | volume = 209 | issue = 2 | pages = 139β51 | date = May 2011 | pmid = 21307119 | doi = 10.1530/JOE-10-0377 | doi-access = }}</ref> Depending on the integrin's regulatory impact on specific receptor tyrosine kinases, the cell can experience: * [[cell growth]]<ref name=":0">{{cite book | vauthors = Bostwick DG, Cheng L | chapter = 9 - Neoplasms of the Prostate|date=2020-01-01 | title = Urologic Surgical Pathology | edition = Fourth |pages=415β525.e42| veditors = Cheng L, MacLennan GT, Bostwick DG |place=Philadelphia|publisher=Content Repository Only!|language=en|isbn=978-0-323-54941-7 }}</ref> * [[cell division]]<ref name=":0" /> * cell survival<ref name=":0" /> * [[cellular differentiation]] * [[apoptosis|apoptosis (programmed cell death)]] Knowledge of the relationship between integrins and receptor tyrosine kinase has laid a foundation for new approaches to cancer therapy. Specifically, targeting integrins associated with RTKs is an emerging approach for inhibiting angiogenesis.<ref>{{cite journal | vauthors = Carbonell WS, DeLay M, Jahangiri A, Park CC, Aghi MK | title = Ξ²1 integrin targeting potentiates antiangiogenic therapy and inhibits the growth of bevacizumab-resistant glioblastoma | journal = Cancer Research | volume = 73 | issue = 10 | pages = 3145β54 | date = May 2013 | pmid = 23644530 | pmc = 4040366 | doi = 10.1158/0008-5472.CAN-13-0011 }}</ref> [[File:Figure 1 - Nieuwenhuis et al 2018 - Integrins promote axonal regeneration after injury of the nervous system - Biological Reviews - doi 10.1111-brv.12398.jpg|thumb|Integrins are localised at the growth cone of regenerating neurons.<ref name="Nieuwenhuis2018a" />]]
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