Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene

Selma Pennacchietti, Paolo Michieli, Maria Galluzzo, Massimiliano Mazzone, Silvia Giordano, Paolo M. Comoglio

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)347-361
Number of pages15
JournalCancer Cell
Volume3
Issue number4
DOIs
Publication statusPublished - Apr 2003

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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