2q31.1

CD49f,ITGA6B,VLA-6

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).

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).

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.

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.