Genomes and Genes
Summary: An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
- Lobert V, Brech A, Pedersen N, Wesche J, Oppelt A, Malerød L, et al. Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin-integrin complexes. Dev Cell. 2010;19:148-59 pubmed publisher..Fibronectin and alpha 5 beta 1 integrin therefore are trafficked to lysosomes in a similar way to growth factors and their receptors. ..
- Chen Q, Meng L, Zhu C, Lin L, Lu H, Ding J. ADAM15 suppresses cell motility by driving integrin alpha5beta1 cell surface expression via Erk inactivation. Int J Biochem Cell Biol. 2008;40:2164-73 pubmed publisher..b>Integrin alpha5beta1 has been reported to bind to ADAM15 in an RGD-dependent manner, but the biological significance of the ..
- Bell McGuinn K, Matthews C, Ho S, Barve M, Gilbert L, Penson R, et al. A phase II, single-arm study of the anti-?5?1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer. Gynecol Oncol. 2011;121:273-9 pubmed publisher
- Omura Y, Chen Y, Lermand O, Jones M, Duvvi H, Shimotsuura Y. Effects of transcutaneous electrical stimulation (1 pulse/sec) through custom-made disposable surface electrodes covering Omura's ST36 area of both legs on normal cell telomeres, oncogen C-fosAb2, integrin alpha5beta1, chlamydia trachomatis, etc. in . Acupunct Electrother Res. 2010;35:147-85 pubmed..amp; Integrin alpha5beta1 (Integ...
- Morozevich G, Kozlova N, Ushakova N, Preobrazhenskaya M, Berman A. Integrin ?5?1 simultaneously controls EGFR-dependent proliferation and Akt-dependent pro-survival signaling in epidermoid carcinoma cells. Aging (Albany NY). 2012;4:368-74 pubmed..Thus, for the first time, we demonstrated that ?5?1 integrin simultaneously maintains pro-survival signaling via continuous activation of AKT and up-regulates proliferation via activation of EGFR. ..
- Mitra A, Sawada K, Tiwari P, Mui K, Gwin K, Lengyel E. Ligand-independent activation of c-Met by fibronectin and ?(5)?(1)-integrin regulates ovarian cancer invasion and metastasis. Oncogene. 2011;30:1566-76 pubmed publisher..These data suggest that fibronectin promotes ovarian cancer invasion and metastasis through an ?(5)?(1)-integrin/c-Met/FAK/Src-dependent signaling pathway, transducing signals through c-Met in an HGF/SF-independent manner. ..
- Zahn G, Volk K, Lewis G, Vossmeyer D, Stragies R, Heier J, et al. Assessment of the integrin alpha5beta1 antagonist JSM6427 in proliferative vitreoretinopathy using in vitro assays and a rabbit model of retinal detachment. Invest Ophthalmol Vis Sci. 2010;51:1028-35 pubmed publisherTo explore the role of integrin alpha5beta1 in proliferative vitreoretinopathy (PVR) pathogenesis by evaluating the expression alpha5beta1 on ARPE-19 cells and patient proliferative membranes, quantifying the inhibitory effects of JSM6427 ..
- Hutton M, Kaparakis Liaskos M, Turner L, Cardona A, Kwok T, Ferrero R. Helicobacter pylori exploits cholesterol-rich microdomains for induction of NF-kappaB-dependent responses and peptidoglycan delivery in epithelial cells. Infect Immun. 2010;78:4523-31 pubmed publisher..pylori. These data implicate cholesterol-rich microdomains as a novel platform for TFSS-dependent delivery of bacterial products to cytosolic pathogen recognition molecules. ..
- Lee B, Clarke D, Al Ahmad A, Kahle M, Parham C, Auckland L, et al. Perlecan domain V is neuroprotective and proangiogenic following ischemic stroke in rodents. J Clin Invest. 2011;121:3005-23 pubmed publisher..These results suggest that perlecan domain V represents a promising approach for stroke treatment. ..
- Yan L, Lin B, Zhu L, Hao Y, Qi Y, Wang C, et al. Enhancement of the adhesive and spreading potentials of ovarian carcinoma RMG-1 cells due to increased expression of integrin alpha5beta1 with the Lewis Y-structure on transfection of the alpha1,2-fucosyltransferase gene. Biochimie. 2010;92:852-7 pubmed publisher..the relative expression of Le(Y) in RMG-1-hFUT cells was about 20-fold that in RMG-1 cells, and that of integrin alpha5beta1 and an integrin-mediated signal transduction molecule, focal adhesion kinase, was also increased in RMG-1-..
- Marchetti G, Escuin S, van der Flier A, De Arcangelis A, Hynes R, Georges Labouesse E. Integrin alpha5beta1 is necessary for regulation of radial migration of cortical neurons during mouse brain development. Eur J Neurosci. 2010;31:399-409 pubmed publisher..Overall, these results indicate that alpha5beta1 integrin functions in the regulation of neural morphology and migration during cortical development, playing a role in cortical lamination. ..
- Dozynkiewicz M, Jamieson N, MacPherson I, Grindlay J, van den Berghe P, von Thun A, et al. Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Dev Cell. 2012;22:131-45 pubmed publisher..The identification of CLIC3 as a regulator of a recycling pathway and as an independent prognostic indicator in PDAC highlights the importance of active integrin trafficking as a potential drive to cancer progression in vivo. ..
- Li L, Welser J, Milner R. Absence of the alpha v beta 3 integrin dictates the time-course of angiogenesis in the hypoxic central nervous system: accelerated endothelial proliferation correlates with compensatory increases in alpha 5 beta 1 integrin expression. J Cereb Blood Flow Metab. 2010;30:1031-43 pubmed publisher
- Mould A, Koper E, Byron A, Zahn G, Humphries M. Mapping the ligand-binding pocket of integrin alpha5beta1 using a gain-of-function approach. Biochem J. 2009;424:179-89 pubmed publisherb>Integrin alpha5beta1 is a key receptor for the extracellular matrix protein fibronectin. Antagonists of human integrin alpha5beta1 have therapeutic potential as anti-angiogenic agents in cancer and diseases of the eye...
- Morgan M, Hamidi H, Bass M, Warwood S, Ballestrem C, Humphries M. Syndecan-4 phosphorylation is a control point for integrin recycling. Dev Cell. 2013;24:472-85 pubmed publisher..These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration. ..
- Muether P, Dell S, Kociok N, Zahn G, Stragies R, Vossmeyer D, et al. The role of integrin alpha5beta1 in the regulation of corneal neovascularization. Exp Eye Res. 2007;85:356-65 pubmed..Integrin alpha(5)beta(1) inhibitors could become a new approach for treatment of neovascularization in the eye. ..
- Valdembri D, Caswell P, Anderson K, Schwarz J, König I, Astanina E, et al. Neuropilin-1/GIPC1 signaling regulates alpha5beta1 integrin traffic and function in endothelial cells. PLoS Biol. 2009;7:e25 pubmed publisher..Nrp1 modulation of alpha5beta1 integrin function can play a causal role in the generation of angiogenesis defects observed in Nrp1 null mice. ..
- Li R, Maminishkis A, Zahn G, Vossmeyer D, Miller S. Integrin alpha5beta1 mediates attachment, migration, and proliferation in human retinal pigment epithelium: relevance for proliferative retinal disease. Invest Ophthalmol Vis Sci. 2009;50:5988-96 pubmed publisherThe aim of this study was to determine the expression and localization of integrin alpha5beta1 in human retinal pigment epithelium (RPE) and its ability to modulate RPE cell attachment, proliferation, migration, and F-actin cytoskeleton ..
- White D, Caswell P, Norman J. alpha v beta3 and alpha5beta1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration. J Cell Biol. 2007;177:515-25 pubmed
- Bass M, Williamson R, Nunan R, Humphries J, Byron A, Morgan M, et al. A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis. Dev Cell. 2011;21:681-93 pubmed publisher..Thus, this syndecan-4-regulated integrin endocytic pathway appears to play a key role in tissue repair. ..
- Liu L, He B, Liu W, Zhou D, Cox J, Zhang X. Tetraspanin CD151 promotes cell migration by regulating integrin trafficking. J Biol Chem. 2007;282:31631-42 pubmed..In conclusion, the YXXvarphi motif-mediated internalization of CD151 promotes integrin-dependent cell migration by modulating the endocytosis and/or vesicular trafficking of its associated integrins. ..
- Caswell P, Spence H, Parsons M, White D, Clark K, Cheng K, et al. Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev Cell. 2007;13:496-510 pubmed..These data indicate that Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix. ..
- Färber K, Synowitz M, Zahn G, Vossmeyer D, Stragies R, Van Rooijen N, et al. An alpha5beta1 integrin inhibitor attenuates glioma growth. Mol Cell Neurosci. 2008;39:579-85 pubmed publisher..We could demonstrate the expression of integrin alpha5beta1 on both microglia and glioma cells using flow cytometry...
- Nam J, Onodera Y, Bissell M, Park C. Breast cancer cells in three-dimensional culture display an enhanced radioresponse after coordinate targeting of integrin alpha5beta1 and fibronectin. Cancer Res. 2010;70:5238-48 pubmed publisher..Our findings offer preclinical validation of fibronectin and alpha5beta1-integrin as targets for breast cancer therapy. ..
- Martin S, Cosset E, Terrand J, Maglott A, Takeda K, Dontenwill M. Caveolin-1 regulates glioblastoma aggressiveness through the control of alpha(5)beta(1) integrin expression and modulates glioblastoma responsiveness to SJ749, an alpha(5)beta(1) integrin antagonist. Biochim Biophys Acta. 2009;1793:354-67 pubmed publisher..Mediator of caveolin-1 effects, alpha(5)beta(1) integrin, is also a marker for glioma aggressiveness and an efficient target for the treatment of glioma especially the ones exerting the highest aggressive phenotype. ..
- Friedland J, Lee M, Boettiger D. Mechanically activated integrin switch controls alpha5beta1 function. Science. 2009;323:642-4 pubmed publisher..In the context of tissues, this integrin switch connects cytoskeleton and extracellular matrix mechanics to adhesion-dependent motility and signaling pathways. ..
- Muller P, Caswell P, Doyle B, Iwanicki M, Tan E, Karim S, et al. Mutant p53 drives invasion by promoting integrin recycling. Cell. 2009;139:1327-41 pubmed publisher..These findings open the possibility that blocking alpha5/beta1-integrin and/or the EGF receptor will have therapeutic benefit in mutant p53-expressing cancers. ..
- Lee M, Huang J, Chen Y, Aplin J, Wu Y, Chen C, et al. Angiogenesis in differentiated placental multipotent mesenchymal stromal cells is dependent on integrin alpha5beta1. PLoS ONE. 2009;4:e6913 pubmed publisher..These results suggest that differentiated hPMSCs may contribute to blood vessel formation, and this activity depends on integrin alpha(5)beta(1). ..
- Stanchi F, Grashoff C, Nguemeni Yonga C, Grall D, Fassler R, Van Obberghen Schilling E. Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation. J Cell Sci. 2009;122:1800-11 pubmed publisher..We propose a model in which the C-terminal domain of ILK promotes integrin sorting by reinforcing alpha5beta1-integrin-actin linkage and controls force transmission by targeting tensin to maturing adhesions. ..
- Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, et al. Helicobacter exploits integrin for type IV secretion and kinase activation. Nature. 2007;449:862-6 pubmed..protein is a specialized adhesin that is targeted to the pilus surface, where it binds to and activates integrin alpha5beta1 receptor on gastric epithelial cells through an arginine-glycine-aspartate motif...
- Bhaskar V, Zhang D, Fox M, Seto P, Wong M, Wales P, et al. A function blocking anti-mouse integrin alpha5beta1 antibody inhibits angiogenesis and impedes tumor growth in vivo. J Transl Med. 2007;5:61 pubmed..The integrin alpha5beta1 has been shown to play a critical role during angiogenesis...
- Ricart A, Tolcher A, Liu G, Holen K, Schwartz G, Albertini M, et al. Volociximab, a chimeric monoclonal antibody that specifically binds alpha5beta1 integrin: a phase I, pharmacokinetic, and biological correlative study. Clin Cancer Res. 2008;14:7924-9 pubmed publisher..Volociximab can be safely administered at 15 mg/kg i.v. per week. The absence of severe toxicities and preliminary activity at the highest dose level warrants further disease-directed studies. ..
- Bass M, Morgan M, Roach K, Settleman J, Goryachev A, Humphries M. p190RhoGAP is the convergence point of adhesion signals from alpha 5 beta 1 integrin and syndecan-4. J Cell Biol. 2008;181:1013-26 pubmed publisher..This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion. ..
- Zech T, Calaminus S, Caswell P, Spence H, Carnell M, Insall R, et al. The Arp2/3 activator WASH regulates ?5?1-integrin-mediated invasive migration. J Cell Sci. 2011;124:3753-9 pubmed publisher..Thus, we implicate WASH and Arp2/3-driven actin nucleation in receptor recycling leading to invasive motility. ..
- Caicedo Carvajal C, Shinbrot T, Foty R. Alpha5beta1 integrin-fibronectin interactions specify liquid to solid phase transition of 3D cellular aggregates. PLoS ONE. 2010;5:e11830 pubmed publisher..b>Integrin alpha5beta1 and soluble fibronectin (sFN) are key players in cell-ECM force generation and in ECM polymerization...
- Morozevich G, Kozlova N, Cheglakov I, Ushakova N, Berman A. Integrin alpha5beta1 controls invasion of human breast carcinoma cells by direct and indirect modulation of MMP-2 collagenase activity. Cell Cycle. 2009;8:2219-25 pubmed
- Kong F, Garcia A, Mould A, Humphries M, Zhu C. Demonstration of catch bonds between an integrin and its ligand. J Cell Biol. 2009;185:1275-84 pubmed publisher..Thus, catch bond formation appears to involve force-assisted activation of the headpiece but not integrin extension. ..
- Morgan M, Byron A, Humphries M, Bass M. Giving off mixed signals--distinct functions of alpha5beta1 and alphavbeta3 integrins in regulating cell behaviour. IUBMB Life. 2009;61:731-8 pubmed publisher..By considering the GTPase and kinase signalling and trafficking of two such closely-related receptors, we begin to understand how cell migration is coordinated. ..
- Humphries J, Byron A, Bass M, Craig S, Pinney J, Knight D, et al. Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Sci Signal. 2009;2:ra51 pubmed publisher..This proteomics workflow now opens the way to further dissection and systems-level analyses of adhesion signaling. ..
- Tsuda K, Furuta N, Inaba H, Kawai S, Hanada K, Yoshimori T, et al. Functional analysis of alpha5beta1 integrin and lipid rafts in invasion of epithelial cells by Porphyromonas gingivalis using fluorescent beads coated with bacterial membrane vesicles. Cell Struct Funct. 2008;33:123-32 pubmed..gingivalis adhesion to epithelial cells, while the subsequent uptake process requires lipid raft components for actin organization, with Rho GTPase Rac1. ..
- Yeh Y, Chang W, Yang H, Cheng H, Wu J, Sheu B. H. pylori cagL amino acid sequence polymorphism Y58E59 induces a corpus shift of gastric integrin ?5?1 related with gastric carcinogenesis. Mol Carcinog. 2011;50:751-9 pubmed publisher..05). H. pylori CagL amino acid polymorphisms like Y58E59 correlate with a higher risk of GCA, and may regulate a corpus shift of gastric integrin ?5?1 to lead to severe corpus gastritis during gastric carcinogenesis. ..
- Wu C, Li T, Hsu S, Su Y, Kao S, Fong Y, et al. IGF-I enhances ?5?1 integrin expression and cell motility in human chondrosarcoma cells. J Cell Physiol. 2011;226:3270-7 pubmed publisher..Taken together, our results indicated that IGF-I enhances the migration of chondrosarcoma cells by increasing ?5?1 integrin expression through the IGF-I receptor/PI3K/Akt/NF-?B signal transduction pathway...
- Isaji T, Sato Y, Fukuda T, Gu J. N-glycosylation of the I-like domain of beta1 integrin is essential for beta1 integrin expression and biological function: identification of the minimal N-glycosylation requirement for alpha5beta1. J Biol Chem. 2009;284:12207-16 pubmed publisherN-Glycosylation of integrin alpha5beta1 plays a crucial role in cell spreading, cell migration, ligand binding, and dimer formation, but the detailed mechanisms by which N-glycosylation mediates these functions remain unclear...
- Morozevich G, Kozlova N, Cheglakov I, Ushakova N, Preobrazhenskaya M, Berman A. Implication of alpha5beta1 integrin in invasion of drug-resistant MCF-7/ADR breast carcinoma cells: a role for MMP-2 collagenase. Biochemistry (Mosc). 2008;73:791-6 pubmed..These data suggest that alpha5beta1 controls invasion ability of these cells by regulating expression of MMP-2, which involves PI-3K and Erk1/2 protein kinase signaling. ..
- Spicer E, Suckert C, Al Attar H, Marsden M. Integrin alpha5beta1 function is regulated by XGIPC/kermit2 mediated endocytosis during Xenopus laevis gastrulation. PLoS ONE. 2010;5:e10665 pubmed publisher..These data support a model where region specific mesoderm induction acts through kermit2 to regulate the temporally and spatially restricted changes in adhesive properties of the alpha5beta1 integrin through receptor endocytosis...
- Caswell P, Chan M, Lindsay A, McCaffrey M, Boettiger D, Norman J. Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments. J Cell Biol. 2008;183:143-55 pubmed publisher..We conclude that RCP provides a scaffold that promotes the physical association and coordinate trafficking of alpha5beta1 and EGFR1 and that this drives migration of tumor cells into three-dimensional matrices. ..
- Robinson E, Foty R, Corbett S. Fibronectin matrix assembly regulates alpha5beta1-mediated cell cohesion. Mol Biol Cell. 2004;15:973-81 pubmed..These results demonstrate that FN matrix assembly contributes significantly to tissue cohesion and represents an alternative mechanism for regulating tissue architecture. ..
- Gibson R, Craig S, Heenan L, Tournier C, Humphries M. Activation of integrin alpha5beta1 delays apoptosis of Ntera2 neuronal cells. Mol Cell Neurosci. 2005;28:588-98 pubmed..The antibody 12G10 specifically delayed loss of phosphorylation of AKT on serine 473, and GSK-3beta on serine 9, induced by serum withdrawal, suggesting that these kinases are critical sensors of integrin activation on neuronal cells. ..