CELL BIOLOGY Pools of ß-Catenin

Abstract:

The tumor suppressive activity of the cell-cell adhesion protein E-cadherin is thought to occur either by increasing cell adhesion and limiting cell migration or by inhibiting ß-catenin-mediated signaling to the nucleus to suppress proliferation. Gottardi et al. report that when overexpressed in a colon carcinoma cell line, E-cadherin inhibited anchorage-independent growth by altering ß-catenin signaling. By expressing a variety of mutant proteins, the authors determined that the extracellular domain of E-cadherin had no growth inhibitory properties. Thus, the adhesive properties of E-cadherin do not influence growth inhibition. Rather, E-cadherin interacted with a specific subset of cytosolic ß-catenin to alter the expression of target genes that regulate tumorigenesis. This small pool of ß-catenin is also the same fraction that associated with the target transcription factor LEF/TCF. It remains to be seen if cadherins in general suppress tumor progression in other tumor-derived cells by antagonizing ß-catenin signaling activity and what the biochemical nature is of the ß-catenin pool that binds to cadherins.

C. J. Gottardi, E. Wong, B. M. Gumbiner, E-cadherin suppresses cellular transformation by inhibiting ß-catenin signaling in an adhesion-independent manner. J. Cell Biol. 153, 1049-1059 (2001). [Abstract] [Full Text]