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