Cell Biology

Pools of β-Catenin

Science's STKE  05 Jun 2001:
Vol. 2001, Issue 85, pp. tw5
DOI: 10.1126/stke.2001.85.tw5

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 β-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 β-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 β-catenin to alter the expression of target genes that regulate tumorigenesis. This small pool of β-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 β-catenin signaling activity and what the biochemical nature is of the β-catenin pool that binds to cadherins.

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