Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression

Chiara Bardella, Barbara Costa, Piera Maggiora, Salvatore Patane, Martina Olivero, Guglielmina N. Ranzani, Michele De Bortoli, Paolo M. Comoglio, Maria Flavia Di Renzo

Research output: Contribution to journalArticle

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Abstract

RON is a tyrosine kinase receptor that triggers scattering of normal cells and invasive growth of cancer cells on ligand binding. We identified a short RON mRNA, which is expressed in human lung, ovary, tissues of the gastrointestinal tract, and also in several human cancers, including ovarian carcinomas and cell lines from pancreatic carcinomas and leukemias. This transcript encodes a truncated protein (short-form RON; sf-RON), lacking most of the RON receptor extracellular domain but retaining the whole transmembrane and intracellular domains. Sf-RON shows strong intrinsic tyrosine kinase activity and is constitutively phosphorylated. Epithelial cells transduced with sf-RON display an aggressive phenotype; they shift to a nonepithelial morphology, are unable to form aggregates, grow faster in monolayer cultures, show anchorage-independent growth, and become motile. We show that in these cells, E-cadherin expression is lost through a dominant transcriptional repression pathway likely mediated by the transcriptional factor SLUG. Altogether, these data show that expression of a naturally occurring, constitutively active truncated RON kinase results in loss of epithelial phenotype and aggressive behavior and, thus, it might contribute to tumor progression.

Original languageEnglish
Pages (from-to)5154-5161
Number of pages8
JournalCancer Research
Volume64
Issue number15
DOIs
Publication statusPublished - Aug 1 2004

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Cadherins
Cell Adhesion
Protein-Tyrosine Kinases
Neoplasms
Phenotype
Drive
rice bran saccharide
Receptor Protein-Tyrosine Kinases
Growth
Ovarian Neoplasms
Gastrointestinal Tract
Ovary
Leukemia
Phosphotransferases
Epithelial Cells
Ligands
Carcinoma
Cell Line
Lung
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression. / Bardella, Chiara; Costa, Barbara; Maggiora, Piera; Patane, Salvatore; Olivero, Martina; Ranzani, Guglielmina N.; De Bortoli, Michele; Comoglio, Paolo M.; Di Renzo, Maria Flavia.

In: Cancer Research, Vol. 64, No. 15, 01.08.2004, p. 5154-5161.

Research output: Contribution to journalArticle

Bardella, Chiara ; Costa, Barbara ; Maggiora, Piera ; Patane, Salvatore ; Olivero, Martina ; Ranzani, Guglielmina N. ; De Bortoli, Michele ; Comoglio, Paolo M. ; Di Renzo, Maria Flavia. / Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression. In: Cancer Research. 2004 ; Vol. 64, No. 15. pp. 5154-5161.
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