Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility

Adelaide M. Carothers, Sara H. Javid, Amy Moran, Daniel H. Hunt, Mark Redston, Monica M. Bertagnolli

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The Min/+ mouse is a model for APC-dependent colorectal cancer (CRC). We showed that tumorigenesis in this animal was associated with decreased E-cadherin adhesion and increased epidermal growth factor receptor (Egfr) activity in the non-tumor intestinal mucosa. Here, we tested whether these abnormalities correlated with changes in the actin cytoskeleton due to increased Rho-ROCK signaling. We treated Apc+/+ (WT) littermate small intestine with EGTA, an inhibitor of E-cadherin, and with LPA, an RhoA activator; both induced effects on adhesion and kinase activity that mimicked the Min/+ phenotype. GTP-bound Rho was increased in Min/+ enterocytes relative to WT. Since RhoA activity is associated with actomyosin contractility, markers of this signaling cascade were assessed including phosphorylated myosin light chain (MLC), cofilin, Pyk2, Src, and MAPK kinases. The increased actomyosin contractility characterizing Min/+ intestinal tissue was suppressed by the ROCK inhibitor, Y27632, but was inducible in the WT by EGTA or LPA. Finally, ultrastructural imaging revealed changes consistent with actomyosin contractility in Min/+ enterocytes. Thus, the positive regulation of E-cadherin adhesion provided by Apc+ in vivo allows proper negative regulation of Egfr, Src, Pyk2, and MAPK, as well as RhoA activities.

Original languageEnglish (US)
Pages (from-to)387-400
Number of pages14
JournalExperimental Cell Research
Volume312
Issue number4
DOIs
StatePublished - Feb 15 2006
Externally publishedYes

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Actomyosin
Cadherins
Protein-Tyrosine Kinases
Enterocytes
Egtazic Acid
Epidermal Growth Factor Receptor
Actin Depolymerizing Factors
Myosin Light Chains
src-Family Kinases
Mitogen-Activated Protein Kinase Kinases
Intestinal Mucosa
Guanosine Triphosphate
Actin Cytoskeleton
Small Intestine
Colorectal Neoplasms
Carcinogenesis
Phosphotransferases
Phenotype

Keywords

  • Actomyosin contractility
  • APC-dependent colon cancer
  • E-cadherin-mediated cell-cell adhesion
  • MAP kinase
  • RhoA

ASJC Scopus subject areas

  • Cell Biology

Cite this

Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility. / Carothers, Adelaide M.; Javid, Sara H.; Moran, Amy; Hunt, Daniel H.; Redston, Mark; Bertagnolli, Monica M.

In: Experimental Cell Research, Vol. 312, No. 4, 15.02.2006, p. 387-400.

Research output: Contribution to journalArticle

Carothers, Adelaide M. ; Javid, Sara H. ; Moran, Amy ; Hunt, Daniel H. ; Redston, Mark ; Bertagnolli, Monica M. / Deficient E-cadherin adhesion in C57BL/6J-Min/+ mice is associated with increased tyrosine kinase activity and RhoA-dependent actomyosin contractility. In: Experimental Cell Research. 2006 ; Vol. 312, No. 4. pp. 387-400.
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