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 language | English |
|---|---|
| Pages (from-to) | 5154-5161 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 64 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - Aug 1 2004 |
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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 journal › Article
}
TY - JOUR
T1 - Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression
AU - Bardella, Chiara
AU - Costa, Barbara
AU - Maggiora, Piera
AU - Patane, Salvatore
AU - Olivero, Martina
AU - Ranzani, Guglielmina N.
AU - De Bortoli, Michele
AU - Comoglio, Paolo M.
AU - Di Renzo, Maria Flavia
PY - 2004/8/1
Y1 - 2004/8/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-04-0600
DO - 10.1158/0008-5472.CAN-04-0600
M3 - Article
VL - 64
SP - 5154
EP - 5161
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 15
ER -