The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer.
The E-cadherin/catenin protein complex regulates the functional integrity of epithelia by mediating specific intercellular adhesion, Defects in the transmembrane E-cadherin protein play an important role in several human cancer types. E-cadherin-inactivating mutations were mainly found in sporadic lobular breast carcinoma and in both familial and sporadic diffuse gastric carcinoma. Armadillo proteins such as beta-catenin and p120ctn are complexed to the cytoplasmic tail of E-cadherin, whereas the vinculin-related alphaE-catenin protein forms a link to the actin cytoskeleton. The latter shows inactivating deletions in various tumor cell lines. Apparently, both E-cadherin and alphaE-catenin serve as tumor suppressor and invasion suppressor molecules. On the other hand, protein-stabilizing oncogenic mutations of beta-catenin were found at high frequency in particular human tumor types. Mutated beta-catenin protein is imported into the nucleus, and its binding to LEF/TCF transcription factors modulates transcription of intriguing target genes. Also p120ctn was recently found to arrive in the nucleus and to interact with a transcription factor. Furthermore, a wide variety of mechanisms have been described to regulate in a reversible way E-cadherin/catenin-mediated cell adhesion and differentiation. These phenomena appear to be crucial in human cancer development and progression.
Nollet
F
F
Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology (VIB)-University of Gent, Ghent, Belgium.
Berx
G
G
van Roy
F
F
D015820:Cadherins / Q000502:physiology*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D015534:Trans-Activators; D051176:beta Catenin; D000095002:Delta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human