Hypoxia leads to decreased autophosphorylation of the MET receptor but promotes its resistance to tyrosine kinase inhibitors.

ABSTRACT: The receptor tyrosine kinase MET and its ligand, the Hepatocyte Growth Factor/Scattor Factor (HGF/SF), are essential to the migration, morphogenesis, and survival of epithelial cells. In addition, dysregulation of MET signaling has been shown to promote tumor progression and invasion in many cancers. Therefore, HGF/SF and MET are major targets for chemotherapies. Improvement of targeted therapies requires a perfect understanding of tumor microenvironment that strongly modifies half-life, bio-accessibility and thus, efficacy of treatments. In particular, hypoxia is a crucial microenvironmental phenomenon promoting invasion and resistance to treatments. Under hypoxia, MET auto-phosphorylation resulting from ligand stimulation or from receptor overexpression is drastically decreased within mi

SUBMITTER: Mekki MS 

PROVIDER: S-EPMC6007473 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature