Integrin subunit alpha 6
The ITGA6 gene provides instructions for making one part (the α6 subunit) of two proteins known as α6β4 integrin and α6β1 integrin. Integrins are a group of proteins that regulate the attachment of cells to one another (cell-cell adhesion) and to the surrounding network of proteins and other molecules (cell-matrix adhesion). Integrins also transmit chemical signals that regulate cell growth and the activity of certain genes.
The α6β4 integrin protein is found primarily in epithelial cells, which are cells that line the surfaces and cavities of the body. This protein plays a particularly important role in strengthening and stabilizing the skin. It is a component of hemidesmosomes, which are microscopic structures that anchor the outer layer of the skin (the epidermis) to underlying layers. As part of a complex network of proteins in hemidesmosomes, α6β4 integrin helps to hold the layers of skin together.
The other integrin made with the α6 subunit, α6β1 integrin, functions during the formation of organs and tissues before birth. The α6β1 integrin protein has not been as well studied as α6β4 integrin.
2. Health Conditions Related to Genetic Changes
2.1. Epidermolysis Bullosa with Pyloric Atresia
At least five mutations in the ITGA6 gene have been found to cause epidermolysis bullosa with pyloric atresia (EB-PA). In addition to skin blistering, people with EB-PA are born with a life-threatening obstruction of the digestive tract called pyloric atresia. Mutations in the ITGA6 gene account for about 5 percent of all cases of EB-PA.
The ITGA6 gene mutations responsible for EB-PA lead to a loss of functional α6β4 integrin. These mutations alter the normal structure and function of the α6 integrin subunit or prevent cells from producing enough of this subunit. The resulting shortage of functional α6β4 integrin causes cells in the epidermis to be fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, leading to the widespread formation of blisters. It is less clear how mutations in the ITGA6 gene are related to pyloric atresia.
Researchers believe that both α6β1 integrin and α6β4 integrin may play critical roles in the progression of cancerous tumors called carcinomas. These cancers arise in epithelial cells and can affect many tissues and organs, including the breast, lung, liver, prostate, and skin.
Changes in the location and activity of α6β1 integrin and α6β4 integrin within cancer cells are associated with the progression of carcinomas. The integrin proteins activate key signaling molecules, which trigger cancer cells to migrate through the body and invade other tissues. These signals also make cancer cells more resistant to self-destruction (apoptosis).
Recent studies suggest that, in addition to their roles in the progression of existing carcinomas, α6β1 integrin and α6β4 integrin may be involved in the initial formation of these tumors.
3. Other Names for This Gene
Cluster of differentiation antigen 49f
integrin alpha 6
integrin alpha chain, alpha 6
integrin, alpha 6
Lymphocyte antigen CD49F
The entry is from https://medlineplus.gov/genetics/gene/itga6
- Allegra M, Gagnoux-Palacios L, Gache Y, Roques S, Lestringant G, Ortonne JP,Meneguzzi G. Rapid decay of alpha6 integrin caused by a mis-sense mutation in thepropeller domain results in severe junctional epidermolysis bullosa with pyloric atresia. J Invest Dermatol. 2003 Dec;121(6):1336-43.
- Ashton GH, Sorelli P, Mellerio JE, Keane FM, Eady RA, McGrath JA. Alpha 6 beta4 integrin abnormalities in junctional epidermolysis bullosa with pyloricatresia. Br J Dermatol. 2001 Feb;144(2):408-14.
- Chung J, Mercurio AM. Contributions of the alpha6 integrins to breastcarcinoma survival and progression. Mol Cells. 2004 Apr 30;17(2):203-9. Review.
- Chung J, Yoon S, Datta K, Bachelder RE, Mercurio AM. Hypoxia-induced vascular endothelial growth factor transcription and protection from apoptosis aredependent on alpha6beta1 integrin in breast carcinoma cells. Cancer Res. 2004 Jul15;64(14):4711-6.
- Gache Y, Romero-Graillet C, Spadafora A, Lépinard C, Descamps P, Bardon CB,Ortonne JP, Meneguzzi G. A novel homozygous mutation affecting integrin alpha6 ina case of junctional epidermolysis bullosa with pyloric atresia detected in uteroby ultrasound examination. J Invest Dermatol. 1998 Nov;111(5):914-6.
- Lipscomb EA, Mercurio AM. Mobilization and activation of a signaling competentalpha6beta4integrin underlies its contribution to carcinoma progression. CancerMetastasis Rev. 2005 Sep;24(3):413-23. Review.
- Nejjari M, Hafdi Z, Dumortier J, Bringuier AF, Feldmann G, Scoazec JY.alpha6beta1 integrin expression in hepatocarcinoma cells: regulation and role in cell adhesion and migration. Int J Cancer. 1999 Nov 12;83(4):518-25.
- Pulkkinen L, Kimonis VE, Xu Y, Spanou EN, McLean WH, Uitto J. Homozygousalpha6 integrin mutation in junctional epidermolysis bullosa with congenitalduodenal atresia. Hum Mol Genet. 1997 May;6(5):669-74.
- Ruzzi L, Gagnoux-Palacios L, Pinola M, Belli S, Meneguzzi G, D'Alessio M,Zambruno G. A homozygous mutation in the integrin alpha6 gene in junctionalepidermolysis bullosa with pyloric atresia. J Clin Invest. 1997 Jun15;99(12):2826-31.