Altered adhesion features and signal transduction in NRK-49F cells transformed by down-regulation of lysyl oxidase

Monia Giampuzzi, Roberta Oleggini, Armando Di Donato

Research output: Contribution to journalArticle

Abstract

Lysyl oxidase (LOX) down-regulation induced an oncogenic phenotype in NRK-49F. This event was accompanied by a constitutive activation of ras oncogene and down-regulation of PDGF β receptor, among other important phenotypic and molecular modifications. In the present paper we show that ras activation is not accompanied by a constitutive activation of the MAP kinases as expected. Surprisingly, even if MAPK-independent, ras activation was accompanied by a constitutive Ser63 and Ser73 phosphorylation of c-jun, a further downstream target of ras. Although rare, this ras alternative pathway has been described. Since ras alone is seldom able to trigger cell transformation and the transformed phenotype showed clearly an abnormal adhesion pattern, we investigated the main molecules involved in cell-cell adhesion. In fact, we found that β-catenin was up-regulated, escaping the glycogen synthase kinase-3β (GSK-3β) control, through unclear mechanisms. Its nuclear accumulation was accompanied by an up-regulation of cyclin D1, as classically described in the activation of the Wnt/β-catenin signal pathway. We believe that the resulting up-regulation of cyclin D1 acted in synergy with ras to induce the cell transformation.

Original languageEnglish
Pages (from-to)239-244
Number of pages6
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1647
Issue number1-2
DOIs
Publication statusPublished - Apr 11 2003

Keywords

  • β-Catenin
  • C-jun
  • Cell adhesion
  • Lysyl oxidase
  • ras activation
  • Tumor suppressor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics

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