Bench to bedside and back again: molecular mechanisms of alpha-catenin function and roles in tumorigenesis

Semin Cancer Biol. 2008 Feb;18(1):53-64. doi: 10.1016/j.semcancer.2007.08.003. Epub 2007 Sep 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Cytoskeleton / physiology*
  • Actins / metabolism*
  • Animals
  • Apoptosis
  • Cadherins / metabolism
  • Cell Adhesion*
  • Cell Polarity
  • Cell Proliferation
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neoplasm Metastasis
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Signal Transduction
  • alpha Catenin / metabolism*
  • beta Catenin / metabolism

Substances

  • Actins
  • Cadherins
  • Intercellular Signaling Peptides and Proteins
  • alpha Catenin
  • beta Catenin