Bench to bedside and back again: molecular mechanisms of alpha-catenin function and roles in tumorigenesis.
The cadherin/catenin complex, comprised of E-cadherin, beta-catenin and alpha-catenin, is essential for initiating cell-cell adhesion, establishing cellular polarity and maintaining tissue organization. Disruption or loss of the cadherin/catenin complex is common in cancer. As the primary cell-cell adhesion protein in epithelial cells, E-cadherin has long been studied in cancer progression. Similarly, additional roles for beta-catenin in the Wnt signaling pathway has led to many studies of the role of beta-catenin in cancer. Alpha-catenin, in contrast, has received less attention. However, recent data demonstrate novel functions for alpha-catenin in regulating the actin cytoskeleton and cell-cell adhesion, which when perturbed could contribute to cancer progression. In this review, we use cancer data to evaluate molecular models of alpha-catenin function, from the canonical role of alpha-catenin in cell-cell adhesion to non-canonical roles identified following conditional alpha-catenin deletion. This analysis identifies alpha-catenin as a prognostic factor in cancer progression.
Benjamin
Jacqueline M
JM
Department of Biological Sciences, Stanford University, 318 Campus Drive, Stanford, CA 94305-5430, USA.
Nelson
W James
WJ
D008841:Actin Cytoskeleton / Q000502:physiology*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D016764:Cell Polarity; D049109:Cell Proliferation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction; D051178:alpha Catenin / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D036341:Intercellular Signaling Peptides and Proteins; D051178:alpha Catenin; D051176:beta Catenin