E-cadherin engagement stimulates proliferation via Rac1

Wendy F. Liu, Celeste M. Nelson, Dana M. Pirone, Christopher S. Chen

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

E-cadherin has been linked to the suppression of tumor growth and the inhibition of cell proliferation in culture. We observed that progressively decreasing the seeding density of normal rat kidney-52E (NRK-52E) or MCF-10A epithelial cells from confluence, indeed, released cells from growth arrest. Unexpectedly, a further decrease in seeding density so that cells were isolated from neighboring cells decreased proliferation. Experiments using microengineered substrates showed that Ecadherin engagement stimulated the peak in proliferation at intermediate seeding densities, and that the proliferation arrest at high densities did not involve E-cadherin, but rather resulted from a crowding-dependent decrease in cell spreading against the underlying substrate. Rac1 activity, which was induced by E-cadherin engagement specifically at intermediate seeding densities, was required for the cadherin-stimulated proliferation, and the control of Rac1 activation by E-cadherin was mediated by p120-catenin. Together, these findings demonstrate a stimulatory role for E-cadherin in proliferative regulation, and identify a simple mechanism by which cell-cell contact may trigger or inhibit epithelial cell proliferation in different settings.

Original languageEnglish (US)
Pages (from-to)431-441
Number of pages11
JournalJournal of Cell Biology
Volume173
Issue number3
DOIs
StatePublished - May 8 2006

All Science Journal Classification (ASJC) codes

  • Cell Biology

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