ITGA6 (integrin, alpha 6)

2013-04-01   Young Hwa Soung , Jun Chung 

Louisiana State University Health Sciences Center - Shreveport, Dept of Biochemistry, Molecular Biology, 1501 Kings Highway PO Box 33932, Shreveport, LA 71130-3932, USA


Atlas Image
Figure 1. Schematic diagram of ITGA6 location on chromosome 2. Chromosome 2 is represented with banding pattern. ITGA6 is located at 31.1 and ranges from 173292314 to 173371181 on reverse strand. The region surrounding ITGA6 is enlarged. Genes are represented by arrows in the direction of transcription.



ITGA6 (Gene ID: 3655) is located on chromosome 2 at 2q31.1. Gene ranges from 173292314 to 173371181 on the plus strand with a total length of 78870 bp.


The ITGA6 gene has 2 transcript variants encoding two different isoforms. Transcript variant 1 (NCBI Accession NM_001079818) encodes the longer isoform a (NP_001073286) comprised of 25 exons. Transcript variant 2 (NCBI Accession NM_000210.2) encodes the shorter isoform b (NP_000201) comprised of 26 exons which has a distinct C-terminus with an alterative coding exon compared to isoform a.


There are no known pseudogenes.



The integrin alpha6 gene encodes for a protein of 10733 amino acid residues (NP_000201), with a molecular mass of 119,467 kDa (P23229 ; UniProKB). It contains a signal peptide, extracellular domain, transmembrane domain and a cytoplasmic domain.
Atlas Image


The integrin alpha 6subunit consists of a heavy and a light chain linked by a disulfide bond. It forms heterodimers with beta-1 or beta-4 integrin subunits to make α6β1 integrin or α6β4 integrin.


α6β4 integrin is widely expressed in epithelia and in a few other cell types such as thymocytes, fibloblasts, and Schwann cells. α6β1 integrin is expressed in platelets, leukocytes and many epithelial cells.


Cell surface and hemidesmosome (Sonnenberg et al., 1991; Alt et al.,2001; Geuijen and Sonnenberg, 2002).


Both α6β1 integrin and α6β4 integrin are receptors for the laminin family of extracellular matrix proteins. α6β4 integrin in epithelial cells plays an essential role in strengthening and stabilizing the skin tissue through the formation of hemidesmosome (Dowling et al., 1996; Nievers et al., 1999; Sterk et al., 2000). α6β1 integrin contributes to the formation of organs and tissues before birth (Georges-Labouesse et al., 1996; Niculescu et al., 2011). In malignant carcinoma cells, both of these integrins serve as signaling receptors that triggers signaling cascades that enhance survival, invasion and metastasis (reviewed in Mercurio et al., 2001).


Mouse, rat and human homologs of ITGA6 share greater than 90% amino acid identity.



A homozyous 1-bp deletion mutation (791delC) have been identified in an infant with epidermolysis bullosa with pyloric atresia and esophageal stenosis (Ruzzi et al., 1997).

Implicated in

Entity name
Glioblastoma multiforme
Lathia et al identified integrin α6 as a hallmark of glioblastoma stem cells (GSCs) (Lathia et al., 2010). In this study, authors find that integrin α6 is co-expressed with conventional GSC markers such as CD15 and CD133, and localized to the perivascular compartment. However, integrin α6 expression enriches for GSCs lacking CD133 expression. Combining expression of both CD133 and integrin α6 led to higher enrichment of GSCs than CD133 alone did. shRNA mediated knockdown of integrin α6 expression results in a reduction of GSC phenotype such as GSC self renewal and tumor formation. The results suggest that integrin α6 is a promising target for antiglioblastoma therapy.
Glioblastoma Multiforme (GBM) is the most common and malignant primary brain tumor with poor prognosis (Singh et al., 2004). Upon diagonosis, 5 year survival rate is less the 3%. GBM is almost incurable because it is cellular heterogeneous and GBM mass invade functional brain area, which makes impossible for the surgeons to totally remove the cancer tissues. Also, it is resistant to the radiation and other treatments (Stupp et al., 2005). Recently, Integrin α6 garnered a lot of attention as potential candidate for effective glioblastoma therapeutic target due to its high expression in neural stem cells and ability to interact with laminin (Lathia et al., 2010).
Entity name
Breast cancer
Both α6β1 integrin and α6β4 integrin contribute to survival of breast carcinoma cells under stress conditions (Chung et al., 2002; Chung et al., 2004a) through upregulation of VEGF expression, either at the level of transcription or translation. The α6β4 integrin dependent translation of VEGF derives from the ability of this integrin to stimulate AKT/mTOR pathway (Chung et al., 2002). Under hypoxic condition, the α6β1 integrin is required for transcriptional activation of VEGF via HIF-1 (Chung et al., 2004b). α6β4 integrin is implicated in invasion and metastasis of breast carcinoma cells via activation of PI3K/AKT pathway when it is mobilized from hemidesmosome into leading edges (Lipscomb et al., 2005).
It is the most common cancer among women and the second leading cause of cancer deaths of women in US. Breast cancer is 100 times more common in women than in men. Despite of its mortality, it is mostly curable disease when it is detected at early stages. Microarray gene expression analysis defines four distinct sub-types of breast cancer, including hormone receptor (HR) positive luminal A and B, human epidermal growth receptor 2 (HER2/neu)-enriched and basal-like breast cancer (BLBC) (Perou et al., 2000). BLBC represent 17% to 37% of all breast cancers and is one of the most aggressive breast cancer sub-types with poor prognosis (Irvin and Carey, 2008). Expression of α6β4 integrin significantly correlates with BLBC (Lu et al., 2008)
High expression of integrin α6 in women with breast cancer significantly correlated with reduced survival times (Friedrich et al., 1995; Chung et al., 2004a). Co-expression of α6β4 integrin and laminin in breast tumors has been correlated with poor prognosis (Tagliabue et al., 1998). Co-expression of both α6β4 integrin and Net1 (RhoA-specific guanine nucleotide exchange factor) is correlated with a high risk of distant metastasis in patients with hormone receptor-positive tumors (Gilcrease et al., 2009).
Entity name
Epidermolysis bullosa letalis with pyloric atresia (EB-PA)
EB-PA is a rare autosomal recessive genetic disease with a poor progonosis. It represents frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa. EB-PA is caused by defects in ITGA6. The mutations in the genes encoding two subunit polypeptides of the α6β4 integrin (ITGA 6 and ITGA4) have been reported in the patients with EB-PA (Chung and Uitto, 2010).
Mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia are common symptoms that affects the pylorus.
Entity name
Prostate cancer
Integrin α6β1 contributes to migration and invasion of protsate cancer cells through cell surface cleavage of integrin α6 in uPA induced manner (Rabinovitz et al., 1995; Demetriou et al., 2004; Pawar., 2007; Ports et al., 2009).
It is the form of cancer that develops in a gland in the male reproductive system. While a majority of prostate cancer grow slowly, some cases of aggressive prostate cancer involve metastasis to the bones and lymph nodes. Prostate cancer usually occurs in older men. No early symptoms are reported in many cases of prostate cancer, but some patients may experience urinary symptoms and discomfort. Treatment options include surgery, chemotherapy, crytherapy, hormonal therapy, and/or radiation.


Pubmed IDLast YearTitleAuthors
113890952001Protein kinase Cdelta-mediated phosphorylation of alpha6beta4 is associated with reduced integrin localization to the hemidesmosome and decreased keratinocyte attachment.Alt A et al
199456152010Epidermolysis bullosa with pyloric atresia.Chung HJ et al
121051882002Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: a survival mechanism for carcinoma cells.Chung J et al
151790312004Contributions of the alpha6 integrins to breast carcinoma survival and progression.Chung J et al
152564362004Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis are dependent on alpha6beta1 integrin in breast carcinoma cells.Chung J et al
150235412004Extracellular alpha 6 integrin cleavage by urokinase-type plasminogen activator in human prostate cancer.Demetriou MC et al
87078381996Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival.Dowling J et al
78508071995High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival.Friedrichs K et al
86731411996Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice.Georges-Labouesse E et al
124298292002Dynamics of the alpha6beta4 integrin in keratinocytes.Geuijen CA et al
191244842009Coexpression of alpha6beta4 integrin and guanine nucleotide exchange factor Net1 identifies node-positive breast cancer patients at high risk for distant metastasis.Gilcrease MZ et al
190080972008What is triple-negative breast cancer?Irvin WJ Jr et al
204523172010Integrin alpha 6 regulates glioblastoma stem cells.Lathia JD et al
162587292005Mobilization and activation of a signaling competent alpha6beta4integrin underlies its contribution to carcinoma progression.Lipscomb EA et al
182815372008Analysis of integrin beta4 expression in human breast cancer: association with basal-like tumors and prognostic significance.Lu S et al
116847092001EGF-R signaling through Fyn kinase disrupts the function of integrin alpha6beta4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion.Mariotti A et al
115440212001The alpha 6 beta 4 integrin and epithelial cell migration.Mercurio AM et al
209656082011Conditional ablation of integrin alpha-6 in mouse epidermis leads to skin fragility and inflammation.Niculescu C et al
103677271999Biology and function of hemidesmosomes.Nievers MG et al
173031202007Integrin alpha6 cleavage: a novel modification to modulate cell migration.Pawar SC et al
109636022000Molecular portraits of human breast tumours.Perou CM et al
194912582009Extracellular engagement of alpha6 integrin inhibited urokinase-type plasminogen activator-mediated cleavage and delayed human prostate bone metastasis.Ports MO et al
75868061995Integrin alpha 6 expression in human prostate carcinoma cells is associated with a migratory and invasive phenotype in vitro and in vivo.Rabinovitz I et al
91855031997A homozygous mutation in the integrin alpha6 gene in junctional epidermolysis bullosa with pyloric atresia.Ruzzi L et al
155491072004Identification of human brain tumour initiating cells.Singh SK et al
20266541991Integrin alpha 6/beta 4 complex is located in hemidesmosomes, suggesting a major role in epidermal cell-basement membrane adhesion.Sonnenberg A et al
108118352000The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes.Sterk LM et al
157580092005Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.Stupp R et al
95169291998Prognostic value of alpha 6 beta 4 integrin expression in breast carcinomas is affected by laminin production from tumor cells.Tagliabue E et al

Other Information

Locus ID:

NCBI: 3655
MIM: 147556
HGNC: 6142
Ensembl: ENSG00000091409


dbSNP: 3655
ClinVar: 3655
TCGA: ENSG00000091409


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Focal adhesionKEGGko04510
ECM-receptor interactionKEGGko04512
Cell adhesion molecules (CAMs)KEGGko04514
Hematopoietic cell lineageKEGGko04640
Regulation of actin cytoskeletonKEGGko04810
Small cell lung cancerKEGGko05222
Focal adhesionKEGGhsa04510
ECM-receptor interactionKEGGhsa04512
Cell adhesion molecules (CAMs)KEGGhsa04514
Hematopoietic cell lineageKEGGhsa04640
Regulation of actin cytoskeletonKEGGhsa04810
Pathways in cancerKEGGhsa05200
Small cell lung cancerKEGGhsa05222
Hypertrophic cardiomyopathy (HCM)KEGGko05410
Hypertrophic cardiomyopathy (HCM)KEGGhsa05410
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGko05412
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGhsa05412
Dilated cardiomyopathyKEGGko05414
Dilated cardiomyopathyKEGGhsa05414
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Cell surface interactions at the vascular wallREACTOMER-HSA-202733
Basigin interactionsREACTOMER-HSA-210991
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Type I hemidesmosome assemblyREACTOMER-HSA-446107
Extracellular matrix organizationREACTOMER-HSA-1474244
Collagen formationREACTOMER-HSA-1474290
Assembly of collagen fibrils and other multimeric structuresREACTOMER-HSA-2022090
Laminin interactionsREACTOMER-HSA-3000157
Non-integrin membrane-ECM interactionsREACTOMER-HSA-3000171
Syndecan interactionsREACTOMER-HSA-3000170
Integrin cell surface interactionsREACTOMER-HSA-216083

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
204523172010Integrin alpha 6 regulates glioblastoma stem cells.239
197677532009Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.225
179351342008Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line.87
146020712003Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration.85
123643232002Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphavbeta3 and alpha6beta1 in human umbilical vein endothelial cells.82
184511462008CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization.76
129196772003The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration.73
169736012006Integrin beta4 regulates migratory behavior of keratinocytes by determining laminin-332 organization.65
162587292005Mobilization and activation of a signaling competent alpha6beta4integrin underlies its contribution to carcinoma progression.64
169405062006Keratinocyte-secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells.64


Young Hwa Soung ; Jun Chung

ITGA6 (integrin, alpha 6)

Atlas Genet Cytogenet Oncol Haematol. 2013-04-01

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