TY - JOUR
T1 - Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene
AU - Pennacchietti, Selma
AU - Michieli, Paolo
AU - Galluzzo, Maria
AU - Mazzone, Massimiliano
AU - Giordano, Silvia
AU - Comoglio, Paolo M.
PY - 2003/4
Y1 - 2003/4
N2 - Hypoxia unleashes the invasive and metastatic potential of tumor cells by largely unknown mechanisms. The Met tyrosine kinase, a high affinity receptor for hepatocyte growth factor (HGF), plays a crucial role in controlling invasive growth and is often overexpressed in cancer. Here we show that: (1) hypoxia activates transcription of the met protooncogene, resulting in higher levels of Met; (2) hypoxic areas of tumors overexpress Met; (3) hypoxia amplifies HGF signaling; (4) hypoxia synergizes with HGF in inducing invasion; (5) the proinvasive effects of hypoxia are mimicked by Met overexpression; and (6) inhibition of Met expression prevents hypoxia-induced invasive growth. These data show that hypoxia promotes tumor invasion by sensitizing cells to HGF stimulation, providing a molecular basis to explain Met overexpression in cancer.
AB - Hypoxia unleashes the invasive and metastatic potential of tumor cells by largely unknown mechanisms. The Met tyrosine kinase, a high affinity receptor for hepatocyte growth factor (HGF), plays a crucial role in controlling invasive growth and is often overexpressed in cancer. Here we show that: (1) hypoxia activates transcription of the met protooncogene, resulting in higher levels of Met; (2) hypoxic areas of tumors overexpress Met; (3) hypoxia amplifies HGF signaling; (4) hypoxia synergizes with HGF in inducing invasion; (5) the proinvasive effects of hypoxia are mimicked by Met overexpression; and (6) inhibition of Met expression prevents hypoxia-induced invasive growth. These data show that hypoxia promotes tumor invasion by sensitizing cells to HGF stimulation, providing a molecular basis to explain Met overexpression in cancer.
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U2 - 10.1016/S1535-6108(03)00085-0
DO - 10.1016/S1535-6108(03)00085-0
M3 - Article
C2 - 12726861
AN - SCOPUS:0037478437
VL - 3
SP - 347
EP - 361
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 4
ER -