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PMID: 16682529 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

E-cadherin engagement stimulates proliferation via Rac1.

The Journal of cell biology ·Vol. 173 ·No. 3 ·2006-05-08 ·Pages 431-41

Liu WF, Nelson CM, Pirone DM, Chen CS

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 E-cadherin 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.

MeSH Terms
Animals Cadherins/genetics,physiology Catenins Cell Adhesion/genetics,physiology Cell Adhesion Molecules/genetics,metabolism Cell Communication/genetics,physiology Cell Count Cell Line Cell Proliferation Cell Shape/genetics,physiology Contact Inhibition/genetics,physiology Epithelial Cells/cytology,metabolism Humans Models, Biological Mutation Phosphoproteins/genetics,metabolism RNA, Small Interfering/genetics Rats S Phase/genetics,physiology Transfection rac1 GTP-Binding Protein/genetics,metabolism
Chemicals
Cadherins Catenins Cell Adhesion Molecules Phosphoproteins RNA, Small Interfering delta catenin rac1 GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Liu Wendy F
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nelson Celeste M
Pirone Dana M
Chen Christopher S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200510087
Published
2006-05-08
Pages
431-41
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2063843
Subset
IM
Grants
NHLBI NIH HHS · HL 076060 · United States
NHLBI NIH HHS · F32 HL076060 · United States
NIBIB NIH HHS · R01 EB000262 · United States
NIBIB NIH HHS · EB00262 · United States
NHLBI NIH HHS · R01 HL073305 · United States
NHLBI NIH HHS · HL73305 · United States
External Links
PubMed source DOI: 10.1083/jcb.200510087 PMC Full Text View journal details
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