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Gene Review

ITGA6  -  integrin, alpha 6

Homo sapiens

Synonyms: CD49 antigen-like family member F, CD49f, ITGA6B, Integrin alpha-6, VLA-6
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Disease relevance of ITGA6


High impact information on ITGA6

  • In vitro studies have shown that four members of the very late antigen (VLA) integrin family of adhesion molecules, VLA-3, VLA-4, VLA-5, and VLA-6, can bind to invasin [6].
  • The presence of VLA-6, CD44v6, and ICAM-1 on melanoma cells was not associated with clinical outcome [7].
  • In view of the role of the VLA-3 and VLA-6 as laminin receptors, this finding is in line with the production of laminin in active liver disease [8].
  • Expression of the alpha6 beta4 integrin is altered at the dermal-epidermal basement-membrane zone; recently, mutations in the corresponding genes (ITGA6 and ITGB4) have been disclosed in a limited number of patients, premature termination codons in both alleles being characteristic of lethal variants [9].
  • In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals [10].

Biological context of ITGA6


Anatomical context of ITGA6

  • Taken together, these data indicate that p67 LBP is an activation-induced surface structure on memory T cells that, together with VLA-6, mediates cellular adherence to laminin [14].
  • Strong staining of capillaries was obtained in both normal and pathological tissue with antibodies to collagen type IV and its putative receptor VLA-1; laminin and its putative receptor VLA-6; and the common VLA beta 1-subunit [15].
  • In the biopsies from nickel sulphate-induced lesions, the keratinocytes showed a tendency to less VLA-6 expression [16].
  • VLA-6 was identified primarily in the basement membrane of vessels, glandular and surface epithelium in both patient groups [17].
  • In active lesions decreased endothelial cell beta1/VLA-6 could result in their detachment from laminin thereby facilitating leukocyte transvascular migration and blood-brain barrier breakdown [18].

Associations of ITGA6 with chemical compounds


Physical interactions of ITGA6

  • The VLA-2 complex (alpha 2/beta 1) was found to act as collagen receptor on platelets and the VLA-6 complex (alpha 6/beta 1) as laminin receptor [21].

Regulatory relationships of ITGA6

  • We postulated that VLA6 might be involved in neutrophil infiltration because it revealed as the most expressed beta1 integrins among VLA5, VLA4, and VLA3, which also appeared to define subsets within the blood neutrophil population [11].
  • In chronic inactive lesions beta1, VLA-6 and alpha(v) were the same as controls but VLA-1 remained increased [18].

Other interactions of ITGA6

  • Because VLA-5 and VLA-6 both closely resemble the previously defined Ic-IIa platelet protein complex, it is likely that there is more than one platelet "Ic" protein complexed with IIa [22].
  • Specific association of CD63 with the VLA-3 and VLA-6 integrins [23].
  • Approximately one third of the tumors stained positively for VLA6 and CD44, and fewer (27%) were positive for VLA2 [24].
  • When combined, siRNAs against ITGA6, PAI-1, and KISS-1 could mimic the negative effect of siPTHrP on migration, whereas siKISS-1 and siPTHrP similarly reduced the proliferative activity of the cells [25].
  • These findings suggest that VLA-6 and VLA-2 receptors mediate attachment of tumor cells to neoplastic BM material, which, in turn, may endow these cells with an increased ability to invade the extracellular matrix [26].

Analytical, diagnostic and therapeutic context of ITGA6


  1. Pyloric atresia-junctional epidermolysis bullosa syndrome showing novel 594insC/Q425P mutations in integrin beta4 gene (ITGB4). Masunaga, T., Ishiko, A., Takizawa, Y., Kim, S.C., Lee, J.S., Nishikawa, T., Shimizu, H. Exp. Dermatol. (2004) [Pubmed]
  2. Tumour progression and metastatic behaviour in vivo correlates with integrin expression on melanocytic tumours. Schadendorf, D., Gawlik, C., Haney, U., Ostmeier, H., Suter, L., Czarnetzki, B.M. J. Pathol. (1993) [Pubmed]
  3. Differential expression of adhesion molecules in acute leukemia. Reuss-Borst, M.A., Klein, G., Waller, H.D., Müller, C.A. Leukemia (1995) [Pubmed]
  4. Properties of metastasizing and nonmetastasizing human melanoma cells. van Muijen, G.N., Danen, E.H., de Vries, T.J., Quax, P.H., Verheijen, J.H., Ruiter, D.J. Recent Results Cancer Res. (1995) [Pubmed]
  5. In vivo distribution of integrins in renal cell carcinoma: integrin-phenotype alteration in different degrees of tumor differentiation and VLA-2 involvement in tumor metastasis. Anastassiou, G., Duensing, S., Steinhoff, G., Kirchner, H., Ganser, A., Atzpodien, J. Cancer Biother. (1995) [Pubmed]
  6. Very late antigen 4-dependent adhesion and costimulation of resting human T cells by the bacterial beta 1 integrin ligand invasin. Ennis, E., Isberg, R.R., Shimizu, Y. J. Exp. Med. (1993) [Pubmed]
  7. Association with clinical outcome of expression of VLA-4 in primary cutaneous malignant melanoma as well as P-selectin and E-selectin on intratumoral vessels. Schadendorf, D., Heidel, J., Gawlik, C., Suter, L., Czarnetzki, B.M. J. Natl. Cancer Inst. (1995) [Pubmed]
  8. Distribution of the VLA family of integrins in normal and pathological human liver tissue. Volpes, R., van den Oord, J.J., Desmet, V.J. Gastroenterology (1991) [Pubmed]
  9. Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense. Pulkkinen, L., Rouan, F., Bruckner-Tuderman, L., Wallerstein, R., Garzon, M., Brown, T., Smith, L., Carter, W., Uitto, J. Am. J. Hum. Genet. (1998) [Pubmed]
  10. Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia. Pulkkinen, L., Kimonis, V.E., Xu, Y., Spanou, E.N., McLean, W.H., Uitto, J. Hum. Mol. Genet. (1997) [Pubmed]
  11. Transendothelial migration induces rapid expression on neutrophils of granule-release VLA6 used for tissue infiltration. Roussel, E., Gingras, M.C. J. Leukoc. Biol. (1997) [Pubmed]
  12. In vitro adhesion of human epidermal Langerhans cells to laminin and fibronectin occurs through beta 1 integrin receptors. Le Varlet, B., Staquet, M.J., Dezutter-Dambuyant, C., Delorme, P., Schmitt, D. J. Leukoc. Biol. (1992) [Pubmed]
  13. The RGD containing site of the mouse laminin A chain is active for cell attachment, spreading, migration and neurite outgrowth. Tashiro, K., Sephel, G.C., Greatorex, D., Sasaki, M., Shirashi, N., Martin, G.R., Kleinman, H.K., Yamada, Y. J. Cell. Physiol. (1991) [Pubmed]
  14. The nonintegrin laminin binding protein (p67 LBP) is expressed on a subset of activated human T lymphocytes and, together with the integrin very late activation antigen-6, mediates avid cellular adherence to laminin. Canfield, S.M., Khakoo, A.Y. J. Immunol. (1999) [Pubmed]
  15. Immunostaining of human brain capillaries by antibodies to very late antigens. McGeer, P.L., Zhu, S.G., Dedhar, S. J. Neuroimmunol. (1990) [Pubmed]
  16. Expression of adhesion molecules and their ligands in contact allergy. Wahbi, A., Marcusson, J.A., Sundqvist, K.G. Exp. Dermatol. (1996) [Pubmed]
  17. Beta-1 integrin cell adhesion molecules in the endometrium of fertile and infertile women. Klentzeris, L.D., Bulmer, J.N., Trejdosiewicz, L.K., Morrison, L., Cooke, I.D. Hum. Reprod. (1993) [Pubmed]
  18. Endothelial cell integrin laminin receptor expression in multiple sclerosis lesions. Sobel, R.A., Hinojoza, J.R., Maeda, A., Chen, M. Am. J. Pathol. (1998) [Pubmed]
  19. Binding of FimD on Bordetella pertussis to very late antigen-5 on monocytes activates complement receptor type 3 via protein tyrosine kinases. Hazenbos, W.L., van den Berg, B.M., Geuijen, C.W., Mooi, F.R., van Furth, R. J. Immunol. (1995) [Pubmed]
  20. Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules. Grassi, F., Dezutter-Dambuyant, C., McIlroy, D., Jacquet, C., Yoneda, K., Imamura, S., Boumsell, L., Schmitt, D., Autran, B., Debré, P., Hosmalin, A. J. Leukoc. Biol. (1998) [Pubmed]
  21. Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Koretz, K., Schlag, P., Boumsell, L., Möller, P. Am. J. Pathol. (1991) [Pubmed]
  22. Multiple very late antigen (VLA) heterodimers on platelets. Evidence for distinct VLA-2, VLA-5 (fibronectin receptor), and VLA-6 structures. Hemler, M.E., Crouse, C., Takada, Y., Sonnenberg, A. J. Biol. Chem. (1988) [Pubmed]
  23. Specific association of CD63 with the VLA-3 and VLA-6 integrins. Berditchevski, F., Bazzoni, G., Hemler, M.E. J. Biol. Chem. (1995) [Pubmed]
  24. Correlation of very late activation integrin and CD44 expression with extrarenal invasion and metastasis of renal cell carcinomas. Gilcrease, M.Z., Truong, L., Brown, R.W. Hum. Pathol. (1996) [Pubmed]
  25. Parathyroid hormone-related protein regulates tumor-relevant genes in breast cancer cells. Dittmer, A., Vetter, M., Schunke, D., Span, P.N., Sweep, F., Thomssen, C., Dittmer, J. J. Biol. Chem. (2006) [Pubmed]
  26. Differential expression of alpha 6 and alpha 2 very late antigen integrins in the normal, hyperplastic, and neoplastic prostate: simultaneous demonstration of cell surface receptors and their extracellular ligands. Bonkhoff, H., Stein, U., Remberger, K. Hum. Pathol. (1993) [Pubmed]
  27. Novel ITGB4 mutations in a patient with junctional epidermolysis bullosa-pyloric atresia syndrome and altered basement membrane zone immunofluorescence for the alpha6beta4 integrin. Takizawa, Y., Shimizu, H., Nishikawa, T., Hatta, N., Pulkkinen, L., Uitto, J. J. Invest. Dermatol. (1997) [Pubmed]
  28. Adhesion and costimulation of proliferative responses of human gamma delta T cells by interaction of VLA-4 and VLA-5 with fibronectin. Avdalovic, M., Fong, D., Formby, B. Immunol. Lett. (1993) [Pubmed]
  29. Expression and endocytosis of integrin VLA receptors for collagen, fibronectin and laminin by normal human keratinocytes. Le Varlet, B., Staquet, M.J., Dezutter-Dambuyant, C., Gaucherand, M., Schmitt, D. J. Dermatol. Sci. (1991) [Pubmed]
  30. VLA-6 (CDw49f) is an important adhesion molecule in NK cell-mediated cytotoxicity following autologous or allogeneic bone marrow transplantation. Lowdell, M.W., Shamim, F., Hamon, M., Macdonald, I.D., Prentice, H.G. Exp. Hematol. (1995) [Pubmed]
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