α-catenin in the adherens junction complex and the possible implications in cancer

Abstract

The most common malignancy in women of the Western World is breast cancer, which develops from mammary gland epithelium. 30-40% of the patients develop metastatic disease, the primary cause of death. Abnormal E-cadherin expression and disturbed adherens junctions (AJs) are often observed. A disturbance in interaction between proteins in the E-cadherin-catenin complex is one of the main events in both early and late steps of cancer development. AJs have a role in the initiation and stabilization of cell-cell adhesion, regulation of the actin cytoskeleton, intracellular signalling and transcriptional regulation. α-catenin, a protein from the AJ complex, may have a role as a molecular switch that connects the E-cadherin-β-catenin complex to the actin cytoskeleton. Besides its function as a linker, it coordinates actin dynamics and has an influence on cell proliferation, migration, invasion and adhesion. Knockout studies showed that loss of α-catenin leads to compromised AJs and impairment of cell-cell adhesion, increased proliferation and migration. α-catenin is crucial for tissue integrity. Many cancers, such as breast, kidney and skin cancer show mutations in the α-catenin gene, CTNNA1.