ITGB4

The ITGB4 gene provides instructions for making one part (the β4 subunit) of a protein known as an 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 integrin protein made with the β4 subunit is known as α6β4 integrin. This protein is found primarily in epithelial cells, which are cells that line the surfaces and cavities of the body. The α6β4 integrin 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.

epidermolysis bullosa with pyloric atresia - caused by mutations in the ITGB4 gene

At least 60 mutations in the ITGB4 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 ITGB4 gene account for about 80 percent of all cases of EB-PA.

ITGB4 gene mutations alter the normal structure and function of the β4 integrin subunit or prevent cells from producing enough of this subunit. As a result, α6β4 integrin is defective or missing. Mutations that lead to a complete or near-complete loss of α6β4 integrin tend to cause more severe signs and symptoms of EB-PA, while mutations that alter the structure or stability of this protein usually cause milder signs and symptoms. A 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 ITGB4 gene are related to pyloric atresia.

cancers - associated with the ITGB4 gene

Researchers believe that α6β4 integrin may play a critical role 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, colon, and skin.

Changes in the location and activity of α6β4 integrin within cancer cells are associated with the progression of carcinomas. The integrin protein activates 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 its role in the progression of existing carcinomas, α6β4 integrin may be involved in the initial formation of these tumors.