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
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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 -