Abstract
Papillary thyroid carcinomas are characterized by rearrangements of the RET receptor tyrosine kinase generating RET/PTC oncogenes. Here we show that osteopontin (OPN), a secreted glycoprotein, is a major RET/PTC-induced transcriptional target in PC Cl 3 thyroid follicular cells. OPN upregulation depended on the integrity of the RET/PTC kinase and tyrosines Y1015 and Y1062, two major RET/PTC autophosphorylation sites. RET/PTC also induced a strong overexpression of CD44, a cell surface signalling receptor for OPN. Upregulation of CD44 was dependent on RET/PTC Y1062, as well. Constitutive OPN overexpression or treatment with exogenous recombinant OPN sharply increased proliferation, Matrigel invasion and spreading in collagen gels of RET/PTC-transformed PC Cl 3 cells. These effects were impaired by the treatment of PC Cl 3-RET/PTC cells with OPN- and CD44-blocking antibodies. Thus, RET/PTC signalling triggers an autocrine loop involving OPN and CD44 that sustains proliferation and invasion of transfomed PC Cl 3 thyrocytes.
| Original language | English |
|---|---|
| Pages (from-to) | 2188-2196 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 23 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Mar 18 2004 |
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Keywords
- Carcinoma
- Kinase
- Motility
- Ras
- Thyroid
- Tyrosine
ASJC Scopus subject areas
- Cancer Research
- Genetics
- Molecular Biology
Cite this
Autocrine stimulation by osteopontin plays a pivotal role in the expression of the mitogenic and invasive phenotype of RET/PTC-transformed thyroid cells. / Castellone, Maria Domenica; Celetti, Angela; Guarino, Valentina; Cirafici, Anna Maria; Basolo, Fulvio; Giannini, Riccardo; Medico, Enzo; Kruhoffer, Mogens; Orntoft, Torben F.; Curcio, Francesco; Fusco, Alfredo; Melillo, Rosa Marina; Santoro, Massimo.
In: Oncogene, Vol. 23, No. 12, 18.03.2004, p. 2188-2196.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Autocrine stimulation by osteopontin plays a pivotal role in the expression of the mitogenic and invasive phenotype of RET/PTC-transformed thyroid cells
AU - Castellone, Maria Domenica
AU - Celetti, Angela
AU - Guarino, Valentina
AU - Cirafici, Anna Maria
AU - Basolo, Fulvio
AU - Giannini, Riccardo
AU - Medico, Enzo
AU - Kruhoffer, Mogens
AU - Orntoft, Torben F.
AU - Curcio, Francesco
AU - Fusco, Alfredo
AU - Melillo, Rosa Marina
AU - Santoro, Massimo
PY - 2004/3/18
Y1 - 2004/3/18
N2 - Papillary thyroid carcinomas are characterized by rearrangements of the RET receptor tyrosine kinase generating RET/PTC oncogenes. Here we show that osteopontin (OPN), a secreted glycoprotein, is a major RET/PTC-induced transcriptional target in PC Cl 3 thyroid follicular cells. OPN upregulation depended on the integrity of the RET/PTC kinase and tyrosines Y1015 and Y1062, two major RET/PTC autophosphorylation sites. RET/PTC also induced a strong overexpression of CD44, a cell surface signalling receptor for OPN. Upregulation of CD44 was dependent on RET/PTC Y1062, as well. Constitutive OPN overexpression or treatment with exogenous recombinant OPN sharply increased proliferation, Matrigel invasion and spreading in collagen gels of RET/PTC-transformed PC Cl 3 cells. These effects were impaired by the treatment of PC Cl 3-RET/PTC cells with OPN- and CD44-blocking antibodies. Thus, RET/PTC signalling triggers an autocrine loop involving OPN and CD44 that sustains proliferation and invasion of transfomed PC Cl 3 thyrocytes.
AB - Papillary thyroid carcinomas are characterized by rearrangements of the RET receptor tyrosine kinase generating RET/PTC oncogenes. Here we show that osteopontin (OPN), a secreted glycoprotein, is a major RET/PTC-induced transcriptional target in PC Cl 3 thyroid follicular cells. OPN upregulation depended on the integrity of the RET/PTC kinase and tyrosines Y1015 and Y1062, two major RET/PTC autophosphorylation sites. RET/PTC also induced a strong overexpression of CD44, a cell surface signalling receptor for OPN. Upregulation of CD44 was dependent on RET/PTC Y1062, as well. Constitutive OPN overexpression or treatment with exogenous recombinant OPN sharply increased proliferation, Matrigel invasion and spreading in collagen gels of RET/PTC-transformed PC Cl 3 cells. These effects were impaired by the treatment of PC Cl 3-RET/PTC cells with OPN- and CD44-blocking antibodies. Thus, RET/PTC signalling triggers an autocrine loop involving OPN and CD44 that sustains proliferation and invasion of transfomed PC Cl 3 thyrocytes.
KW - Carcinoma
KW - Kinase
KW - Motility
KW - Ras
KW - Thyroid
KW - Tyrosine
UR - http://www.scopus.com/inward/record.url?scp=11144355973&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=11144355973&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1207322
DO - 10.1038/sj.onc.1207322
M3 - Article
C2 - 14981541
AN - SCOPUS:11144355973
VL - 23
SP - 2188
EP - 2196
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 12
ER -