integrin alpha6beta1


Summary: A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.

Top Publications

  1. Le Bellego F, Pisselet C, Huet C, Monget P, Monniaux D. Laminin-alpha6beta1 integrin interaction enhances survival and proliferation and modulates steroidogenesis of ovine granulosa cells. J Endocrinol. 2002;172:45-59 pubmed
    ..It is suggested that during the follicular and the preovulatory phases of the estrous cycle, the increasing levels of LN in GC of large antral follicles might support their final development to ovulation. ..
  2. Almeida E, Huovila A, Sutherland A, Stephens L, Calarco P, Shaw L, et al. Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Cell. 1995;81:1095-104 pubmed
    ..Our results indicate a novel role for the integrin alpha 6 beta 1 as a cell-cell adhesion receptor that mediates sperm-egg binding. ..
  3. Decker L, Ffrench Constant C. Lipid rafts and integrin activation regulate oligodendrocyte survival. J Neurosci. 2004;24:3816-25 pubmed
    ..Together, these results point to an essential role for rafts in oligodendrocyte survival signaling on the basis of the provision of a favorable environment for growth factor-mediated integrin activation. ..
  4. Chen C, Chen N, Lau L. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem. 2001;276:10443-52 pubmed
  5. Kikkawa Y, Sasaki T, Nguyen M, Nomizu M, Mitaka T, Miner J. The LG1-3 tandem of laminin alpha5 harbors the binding sites of Lutheran/basal cell adhesion molecule and alpha3beta1/alpha6beta1 integrins. J Biol Chem. 2007;282:14853-60 pubmed
    ..Our results also suggest that the binding site for Lu/B-CAM on laminin alpha5 may overlap with that of integrins alpha3beta1 and alpha6beta1. ..
  6. Chen M, Tung K, Coonrod S, Takahashi Y, Bigler D, Chang A, et al. Role of the integrin-associated protein CD9 in binding between sperm ADAM 2 and the egg integrin alpha6beta1: implications for murine fertilization. Proc Natl Acad Sci U S A. 1999;96:11830-5 pubmed
    ..Our results suggest that high-avidity binding between fertilin beta (ADAM 2) and alpha6beta1 requires cooperation between alpha6beta1 and CD9. Such cooperation may assist sperm passage into the oviduct as well as sperm-egg interactions. ..
  7. Bajanca F, Luz M, Raymond K, Martins G, Sonnenberg A, Tajbakhsh S, et al. Integrin alpha6beta1-laminin interactions regulate early myotome formation in the mouse embryo. Development. 2006;133:1635-44 pubmed
    ..cells, Myf5-null cells do not express the alpha6beta1 integrin, a laminin receptor, suggesting that integrin alpha6beta1-laminin interactions are required for myotomal laminin matrix assembly...
  8. Inoue O, Suzuki Inoue K, McCarty O, Moroi M, Ruggeri Z, Kunicki T, et al. Laminin stimulates spreading of platelets through integrin alpha6beta1-dependent activation of GPVI. Blood. 2006;107:1405-12 pubmed
    The extracellular matrix protein, laminin, supports platelet adhesion through binding to integrin alpha6beta1 In the present study, we demonstrate that human laminin, purified from placenta, also stimulates formation of filopodia and ..
  9. Delwel G, de Melker A, Hogervorst F, Jaspars L, Fles D, Kuikman I, et al. Distinct and overlapping ligand specificities of the alpha 3A beta 1 and alpha 6A beta 1 integrins: recognition of laminin isoforms. Mol Biol Cell. 1994;5:203-15 pubmed
    ..These results demonstrate that both alpha 3A beta 1 and alpha 6A beta 1 integrins are typical laminin receptors but that their affinity and activation dependence for binding to various laminin isoforms differ considerably. ..

More Information


  1. Reddy V, Rajeev S, Gupta V. Alpha 6 beta 1 Integrin is a potential clinical marker for evaluating sperm quality in men. Fertil Steril. 2003;79 Suppl 3:1590-6 pubmed
    ..The samples with high rate of acrosomal reaction showed a good expression of alpha6beta1 and maximum binding to oocyte in an in vitro binding assay. alpha6beta1 Integrin may be used as a clinical marker to evaluate sperm quality. ..
  2. Leu S, Chen N, Chen C, Todorovic V, Bai T, Juric V, et al. Targeted mutagenesis of the angiogenic protein CCN1 (CYR61). Selective inactivation of integrin alpha6beta1-heparan sulfate proteoglycan coreceptor-mediated cellular functions. J Biol Chem. 2004;279:44177-87 pubmed
    ..A ligand of several integrin receptors, CCN1 acts through integrin alpha6beta1 and heparan sulfate proteoglycans (HSPGs) to promote specific functions in fibroblasts, smooth muscle cells,..
  3. Lin C, Chen C, Leu S, Grzeszkiewicz T, Lau L. Integrin-dependent functions of the angiogenic inducer NOV (CCN3): implication in wound healing. J Biol Chem. 2005;280:8229-37 pubmed
    ..These findings, together with its angiogenic activity, support a role for CCN3 in cutaneous wound healing in skin fibroblasts and establish its matricellular mode of action through integrin receptors. ..
  4. Miller B, Georges Labouesse E, Primakoff P, Myles D. Normal fertilization occurs with eggs lacking the integrin alpha6beta1 and is CD9-dependent. J Cell Biol. 2000;149:1289-96 pubmed
  5. Nishiuchi R, Takagi J, Hayashi M, Ido H, Yagi Y, Sanzen N, et al. Ligand-binding specificities of laminin-binding integrins: a comprehensive survey of laminin-integrin interactions using recombinant alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4 integrins. Matrix Biol. 2006;25:189-97 pubmed
    ..for laminin-332 (alpha3beta3gamma2) and laminin-511 (alpha5beta1gamma1)/521 (alpha5beta2gamma1), while integrin alpha6beta1 showed a broad specificity, binding to all laminin isoforms with a preference for laminin-111 (..
  6. Ziyyat A, Rubinstein E, Monier Gavelle F, Barraud V, Kulski O, Prenant M, et al. CD9 controls the formation of clusters that contain tetraspanins and the integrin alpha 6 beta 1, which are involved in human and mouse gamete fusion. J Cell Sci. 2006;119:416-24 pubmed
    ..Altogether, these data show that CD9 controls the redistribution of some membrane proteins including the alpha 6 beta1 integrin into clusters that may be necessary for gamete fusion. ..
  7. Le Naour F, Rubinstein E, Jasmin C, Prenant M, Boucheix C. Severely reduced female fertility in CD9-deficient mice. Science. 2000;287:319-21 pubmed
    ..Thus, CD9 appears to be essential for sperm-egg fusion, a process involving the CD9-associated integrin alpha6beta1.
  8. Haworth O, Hardie D, Burman A, Rainger G, Eksteen B, Adams D, et al. A role for the integrin alpha6beta1 in the differential distribution of CD4 and CD8 T-cell subsets within the rheumatoid synovium. Rheumatology (Oxford). 2008;47:1329-34 pubmed publisher
    ..We propose that this leads to their retention within the rheumatoid synovium in perivascular cuffs, which are defined and delineated by the expression of laminin. ..
  9. Goel H, Pursell B, Standley C, Fogarty K, Mercurio A. Neuropilin-2 regulates ?6?1 integrin in the formation of focal adhesions and signaling. J Cell Sci. 2012;125:497-506 pubmed publisher
    ..Together, our data reveal a new VEGF-NRP2 signaling pathway that activates the ?6?1 integrin and enables it to form focal adhesions and signal. This pathway is important in the pathogenesis of breast cancer...
  10. Dai J, Dou K, Wang C, Zhao P, Lau W, Tao L, et al. The interaction of HAb18G/CD147 with integrin alpha6beta1 and its implications for the invasion potential of human hepatoma cells. BMC Cancer. 2009;9:337 pubmed publisher
    ..The expression levels of HAb18G/CD147 and integrin alpha6beta1 were determined by immunofluorescent double-staining and confocal imaging analysis...
  11. Sroka I, Anderson T, McDaniel K, Nagle R, Gretzer M, Cress A. The laminin binding integrin alpha6beta1 in prostate cancer perineural invasion. J Cell Physiol. 2010;224:283-8 pubmed publisher
    ..class of proteins line the neural route and tumor cells escaping from the gland express the laminin binding integrin alpha6beta1 as a prominent cell surface receptor...
  12. Ido H, Harada K, Futaki S, Hayashi Y, Nishiuchi R, Natsuka Y, et al. Molecular dissection of the alpha-dystroglycan- and integrin-binding sites within the globular domain of human laminin-10. J Biol Chem. 2004;279:10946-54 pubmed
  13. Sawai H, Funahashi H, Yamamoto M, Okada Y, Hayakawa T, Tanaka M, et al. Interleukin-1alpha enhances integrin alpha(6)beta(1) expression and metastatic capability of human pancreatic cancer. Oncology. 2003;65:167-73 pubmed
    ..Our results indicated that alpha(6)beta(1)-integrin and IL-1RI expression may play important roles in metastasis formation. ..
  14. Ke A, Shi G, Zhou J, Huang X, Shi Y, Ding Z, et al. CD151 amplifies signaling by integrin ?6?1 to PI3K and induces the epithelial-mesenchymal transition in HCC cells. Gastroenterology. 2011;140:1629-41.e15 pubmed publisher
    ..High expression levels of CD151 and ?6 promote invasiveness of HCC cells. Either of these proteins, or PI3K signaling, might be targets for therapeutics for subgroups of patients with HCC. ..
  15. Leu S, Liu Y, Chen N, Chen C, Lam S, Lau L. Identification of a novel integrin alpha 6 beta 1 binding site in the angiogenic inducer CCN1 (CYR61). J Biol Chem. 2003;278:33801-8 pubmed
  16. Baron W, Decker L, Colognato H, Ffrench Constant C. Regulation of integrin growth factor interactions in oligodendrocytes by lipid raft microdomains. Curr Biol. 2003;13:151-5 pubmed
    ..survival by amplification of PDGFalphaR signaling, induces clustering of the laminin binding integrin alpha6beta1 with the PDGFalphaR-containing lipid raft domains...
  17. Grzeszkiewicz T, Lindner V, Chen N, Lam S, Lau L. The angiogenic factor cysteine-rich 61 (CYR61, CCN1) supports vascular smooth muscle cell adhesion and stimulates chemotaxis through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans. Endocrinology. 2002;143:1441-50 pubmed
    ..Together, these results implicate CYR61 as a novel factor that modulates the responses of VSMCs to vascular injury. ..
  18. Imanaka Yoshida K, Enomoto Iwamoto M, Yoshida T, Sakakura T. Vinculin, Talin, Integrin alpha6beta1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix. Cell Motil Cytoskeleton. 1999;42:1-11 pubmed
    ..These findings suggest that vinculin, talin, integrin alpha6beta1 and laminin system can be involved in transmission of contraction force to the extracellular matrix.
  19. Chen M, Almeida E, Huovila A, Takahashi Y, Shaw L, Mercurio A, et al. Evidence that distinct states of the integrin alpha6beta1 interact with laminin and an ADAM. J Cell Biol. 1999;144:549-61 pubmed
    ..We previously provided evidence that the integrin alpha6beta1, on mouse eggs and on alpha6-transfected cells, interacted with the disintegrin domain of the sperm surface ..
  20. Zhang X, Bontrager A, Hemler M. Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PKC to specific beta(1) integrins. J Biol Chem. 2001;276:25005-13 pubmed
  21. Chen N, Chen C, Lau L. Adhesion of human skin fibroblasts to Cyr61 is mediated through integrin alpha 6beta 1 and cell surface heparan sulfate proteoglycans. J Biol Chem. 2000;275:24953-61 pubmed
    ..In addition, these findings suggest that Cyr61 might elicit disparate biological effects in different cell types through interaction with distinct integrin receptors. ..
  22. Sixt M, Hallmann R, Wendler O, Scharffetter Kochanek K, Sorokin L. Cell adhesion and migration properties of beta 2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation. J Biol Chem. 2001;276:18878-87 pubmed
  23. Laursen L, Chan C, Ffrench Constant C. An integrin-contactin complex regulates CNS myelination by differential Fyn phosphorylation. J Neurosci. 2009;29:9174-85 pubmed publisher
    ..We conclude, therefore, that a novel integrin/contactin complex coordinates signals from extracellular matrix and the axonal surface to regulate both oligodendrocyte survival and myelination by controlling Fyn activity. ..
  24. Staquicini F, Dias Neto E, Li J, Snyder E, Sidman R, Pasqualini R, et al. Discovery of a functional protein complex of netrin-4, laminin gamma1 chain, and integrin alpha6beta1 in mouse neural stem cells. Proc Natl Acad Sci U S A. 2009;106:2903-8 pubmed publisher
    ..Our findings present a unique molecular mechanism mediating astrocytic/neuronal crosstalk that regulates ongoing neurogenesis in the adult olfactory system. ..
  25. Evans J. Sperm disintegrins, egg integrins, and other cell adhesion molecules of mammalian gamete plasma membrane interactions. Front Biosci. 1999;4:D114-31 pubmed
  26. Miyado K, Yamada G, Yamada S, Hasuwa H, Nakamura Y, Ryu F, et al. Requirement of CD9 on the egg plasma membrane for fertilization. Science. 2000;287:321-4 pubmed
    ..When sperm were injected into oocytes with assisted microfertilization techniques, however, the fertilized eggs developed to term. These results indicate that CD9 has a crucial role in sperm-egg fusion. ..
  27. Kikkawa Y, Sanzen N, Fujiwara H, Sonnenberg A, Sekiguchi K. Integrin binding specificity of laminin-10/11: laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins. J Cell Sci. 2000;113 ( Pt 5):869-76 pubmed
    ..These results indicated that laminin-10/11 are potent and versatile adhesive ligands in basement membranes capable of binding to both alpha 3 beta 1 and alpha 6 beta 1 integrins with high avidity and also to alpha 6 beta 4 integrin. ..
  28. Chen H, Sampson N. Mediation of sperm-egg fusion: evidence that mouse egg alpha6beta1 integrin is the receptor for sperm fertilinbeta. Chem Biol. 1999;6:1-10 pubmed
    ..We conclude that fertilinbeta binds directly to the alpha6beta1 integrin on the egg surface and this partnership mediates sperm-egg fusion. ..
  29. Carloni V, Mazzocca A, Pantaleo P, Cordella C, Laffi G, Gentilini P. The integrin, alpha6beta1, is necessary for the matrix-dependent activation of FAK and MAP kinase and the migration of human hepatocarcinoma cells. Hepatology. 2001;34:42-9 pubmed
    ..Moreover, the expression of alpha6beta1 in HCC cells is necessary for FAK/MAP kinase-dependent migration. ..
  30. Leu S, Lam S, Lau L. Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphavbeta3 and alpha6beta1 in human umbilical vein endothelial cells. J Biol Chem. 2002;277:46248-55 pubmed
  31. Colognato H, Ramachandrappa S, Olsen I, Ffrench Constant C. Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. J Cell Biol. 2004;167:365-75 pubmed
  32. Oikawa Y, Hansson J, Sasaki T, Rousselle P, Domogatskaya A, Rodin S, et al. Melanoma cells produce multiple laminin isoforms and strongly migrate on ?5 laminin(s) via several integrin receptors. Exp Cell Res. 2011;317:1119-33 pubmed publisher
  33. Chang J, Chang H, Lin C, Lo S. The integrin alpha6beta1 modulation of PI3K and Cdc42 activities induces dynamic filopodium formation in human platelets. J Biomed Sci. 2005;12:881-98 pubmed
    ..In contrast, activation via integrin alpha6beta1 is less well studied...
  34. Fenczik C, Sethi T, Ramos J, Hughes P, Ginsberg M. Complementation of dominant suppression implicates CD98 in integrin activation. Nature. 1997;390:81-5 pubmed publisher
    ..These data indicate that CD98 is involved in regulating integrin affinity, and validate an unbiased genetic approach to analysing integrin signalling pathways...
  35. Serru V, Le Naour F, Billard M, Azorsa D, Lanza F, Boucheix C, et al. Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions. Biochem J. 1999;340 ( Pt 1):103-11 pubmed
    ..Because all tetraspan-tetraspan associations are disrupted by digitonin, it is likely that the other tetraspans interact indirectly with integrins, through interactions with CD81 or CD151. ..
  36. Zhang X, Kazarov A, Yang X, Bontrager A, Stipp C, Hemler M. Function of the tetraspanin CD151-alpha6beta1 integrin complex during cellular morphogenesis. Mol Biol Cell. 2002;13:1-11 pubmed
    ..Also, antibodies to alpha6beta1 and CD151 inhibited formation of endothelial cell cord-like networks, thus pointing to possible relevance of CD151-alpha6beta1 complexes during angiogenesis. ..
  37. Sterk L, Geuijen C, Van Den Berg J, Claessen N, Weening J, Sonnenberg A. Association of the tetraspanin CD151 with the laminin-binding integrins alpha3beta1, alpha6beta1, alpha6beta4 and alpha7beta1 in cells in culture and in vivo. J Cell Sci. 2002;115:1161-73 pubmed
    ..These results suggest that the interactions between CD151 and laminin-binding integrins are subject to cell-type-specific regulation. ..
  38. Bello DeOcampo D, Kleinman H, Deocampo N, Webber M. Laminin-1 and alpha6beta1 integrin regulate acinar morphogenesis of normal and malignant human prostate epithelial cells. Prostate. 2001;46:142-53 pubmed
    ..This novel 3D cell culture model is useful for elucidating regulation of acinar morphogenesis and its loss during prostate carcinogenesis. ..
  39. Delamarre E, Taboubi S, Mathieu S, Berenguer C, Rigot V, Lissitzky J, et al. Expression of integrin alpha6beta1 enhances tumorigenesis in glioma cells. Am J Pathol. 2009;175:844-55 pubmed publisher
    The integrin alpha6beta1 and its main ligand laminin-111 are overexpressed in glioblastoma, as compared with normal brain tissue, suggesting they may be involved in glioblastoma malignancy...
  40. Hsu P, Su B, Kuok Q, Mo F. Extracellular matrix protein CCN1 regulates cardiomyocyte apoptosis in mice with stress-induced cardiac injury. Cardiovasc Res. 2013;98:64-72 pubmed publisher
    ..CCN1 increases cellular susceptibility to Fas-induced apoptosis by increasing ROS and cell-surface Fas expression. ..
  41. Morrison B, Jose C, Cutler M. Connective Tissue Growth Factor (CTGF/CCN2) enhances lactogenic differentiation of mammary epithelial cells via integrin-mediated cell adhesion. BMC Cell Biol. 2010;11:35 pubmed publisher
    ..The mechanisms by which CTGF/CCN2 contributed to lactogenic differentiation include direct binding of CTGF/CCN2 to integrin complexes and CTGF/CCN2-induced matrix protein expression resulting in elevated integrin functionality. ..
  42. Chang C, Goel H, Gao H, Pursell B, Shultz L, Greiner D, et al. A laminin 511 matrix is regulated by TAZ and functions as the ligand for the α6Bβ1 integrin to sustain breast cancer stem cells. Genes Dev. 2015;29:1-6 pubmed publisher
    ..We observed that TAZ regulates the transcription of the α5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer. ..
  43. Huang Z, Miao X, Patarroyo M, Nilsson G, Pernow J, Li N. Tetraspanin CD151 and integrin α6β1 mediate platelet-enhanced endothelial colony forming cell angiogenesis. J Thromb Haemost. 2016;14:606-18 pubmed publisher
    ..Platelet-enhanced ECFC angiogenesis requires platelet tetraspanin CD151 and α6β1 integrin, as well as ECFC α6β1 integrin and Src-PI3K signaling. ..
  44. Shen Q, Wang Y, Kokovay E, Lin G, Chuang S, Goderie S, et al. Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell. 2008;3:289-300 pubmed publisher
  45. David R, Shai E, Aframian D, Palmon A. Isolation and cultivation of integrin alpha(6)beta(1)-expressing salivary gland graft cells: a model for use with an artificial salivary gland. Tissue Eng Part A. 2008;14:331-7 pubmed publisher
    ..6-fold and 3 fold, respectively. We believe that SGIE graft cells may be suitable candidates for future tissue-engineered SGs that have been damaged by irradiation in patients with head and neck cancer. ..
  46. Barraud Lange V, Naud Barriant N, Saffar L, Gattegno L, Ducot B, Drillet A, et al. Alpha6beta1 integrin expressed by sperm is determinant in mouse fertilization. BMC Dev Biol. 2007;7:102 pubmed
    ..This hypothesis is further supported by the exchange of membrane fragments occurring between gametes prior to fusion that we recently reported. ..
  47. Bosco D, Meda P, Halban P, Rouiller D. Importance of cell-matrix interactions in rat islet beta-cell secretion in vitro: role of alpha6beta1 integrin. Diabetes. 2000;49:233-43 pubmed
  48. Chainani Wu N, Lagenaur L, Penaranda M, Palefsky J. Integrin expression in oral hairy leukoplakia and normal tongue epithelium. Oral Dis. 2000;6:234-40 pubmed
    ..To describe the expression of integrins in the epithelium of oral hairy leukoplakia (HL) and compare to that of normal lateral tongue epithelium...
  49. Larrieu Lahargue F, Welm A, Thomas K, Li D. Netrin-4 activates endothelial integrin {alpha}6{beta}1. Circ Res. 2011;109:770-4 pubmed publisher
    ..The ?6?1 integrin is a netrin-4 receptor in lymphatic endothelium and consequently represents a potential target to inhibit netrin-4-induced metastatic dissemination. ..
  50. Pirila L, Aho H, Roivainen A, Konttinen Y, Pelliniemi L, Heino J. Identification of alpha6beta1 integrin positive cells in synovial lining layer as type B synoviocytes. J Rheumatol. 2001;28:478-84 pubmed
    ..b>Integrin alpha6beta1 is known to be a laminin receptor of endothelial cells, adipocytes, and macrophages, not usually expressed ..
  51. Gonzalez A, Gonzales M, Herron G, Nagavarapu U, Hopkinson S, Tsuruta D, et al. Complex interactions between the laminin alpha 4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo. Proc Natl Acad Sci U S A. 2002;99:16075-80 pubmed
    ..We propose a model based on these data that reconcile apparent discrepancies in the recent literature with regard to the role of the alphavbeta3 integrin in angiogenesis. ..
  52. Kazarov A, Yang X, Stipp C, Sehgal B, Hemler M. An extracellular site on tetraspanin CD151 determines alpha 3 and alpha 6 integrin-dependent cellular morphology. J Cell Biol. 2002;158:1299-309 pubmed
  53. Calzada M, Sipes J, Krutzsch H, Yurchenco P, Annis D, Mosher D, et al. Recognition of the N-terminal modules of thrombospondin-1 and thrombospondin-2 by alpha6beta1 integrin. J Biol Chem. 2003;278:40679-87 pubmed