TY - JOUR
T1 - A microRNA code for prostate cancer metastasis
AU - Bonci, Désirée
AU - Coppola, Valeria
AU - Patrizii, Michele
AU - Addario, Antonio
AU - Cannistraci, A.
AU - Francescangeli, Federica
AU - Pecci, R.
AU - Muto, G.
AU - Collura, Devis
AU - Bedini, R.
AU - Zeuner, A.
AU - Valtieri, Mauro
AU - Sentinelli, S.
AU - Benassi, Maria Serena
AU - Gallucci, Michele
AU - Carlini, Paolo
AU - Piccolo, Stefano
AU - De Maria, Ruggero Marchiano
PY - 2016/3/3
Y1 - 2016/3/3
N2 - Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-β and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.
AB - Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-β and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.
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U2 - 10.1038/onc.2015.176
DO - 10.1038/onc.2015.176
M3 - Article
VL - 35
SP - 1180
EP - 1192
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 9
ER -