p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression

Edwin Soto, Masahiro Yanagisawa, Laura A. Marlow, John A III Copland, Edith A. Perez, Panagiotis Z Anastasiadis

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

p120 catenin regulates the activity of the Rho family guanosine triphosphatases (including RhoA and Rac1) in an adhesion-dependent manner. Through this action, p120 promotes a sessile cellular phenotype when associated with epithelial cadherin (E-cadherin) or a motile phenotype when associated with mesenchymal cadherins. In this study, we show that p120 also exerts signifi cant and diametrically opposing effects on tumor cell growth depending on E-cadherin expression. Endogenous p120 acts to stabilize E-cadherin complexes and to actively promote the tumor-suppressive function of E-cadherin, potently inhibiting Ras activation. Upon E-cadherin loss during tumor progression, the negative regulation of Ras is relieved; under these conditions, endogenous p120 promotes transformed cell growth both in vitro and in vivo by activating a Rac1 - mitogen-activated protein kinase signaling pathway normally activated by the adhesion of cells to the extracellular matrix. These data indicate that both E-cadherin and p120 are important regulators of tumor cell growth and imply roles for both proteins in chemoresistance and targeted therapeutics.

Original languageEnglish (US)
Pages (from-to)737-749
Number of pages13
JournalJournal of Cell Biology
Volume183
Issue number4
DOIs
StatePublished - Nov 17 2008

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Cadherins
Growth
Neoplasms
Phenotype
Guanosine
delta catenin
Mitogen-Activated Protein Kinases
Cell Adhesion
Extracellular Matrix
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression. / Soto, Edwin; Yanagisawa, Masahiro; Marlow, Laura A.; Copland, John A III; Perez, Edith A.; Anastasiadis, Panagiotis Z.

In: Journal of Cell Biology, Vol. 183, No. 4, 17.11.2008, p. 737-749.

Research output: Contribution to journalArticle

Soto, Edwin ; Yanagisawa, Masahiro ; Marlow, Laura A. ; Copland, John A III ; Perez, Edith A. ; Anastasiadis, Panagiotis Z. / p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression. In: Journal of Cell Biology. 2008 ; Vol. 183, No. 4. pp. 737-749.
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AU - Anastasiadis, Panagiotis Z

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