title: MET deregulation in breast cancer.
abstract: BACKGROUND
  Mesenchymal-epithelial transition (MET) is an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). MET has a normal function in organ development during embryogenesis and in tissue homeostasis during adult life. Deregulation of HGF/MET signaling pathway is frequently observed in many cancer types, conferring invasive growth and tendency to progression. MET deregulation is due to gene amplification or increased copy number, gene mutation, receptor over-expression or ligand autocrine loops activation. These events lead to migration, invasion, proliferation, metastatic spread and neo-angiogenesis of cancer cells, suggesting that anti-HGF/MET agents may represent a potential antitumor strategy. In breast cancer (BC), preclinical and clinical data demonstrated the role of HGF/MET signalling pathway in carcinogenesis, disease progression and resistance features.
  
  
  METHODS
  For this review article, all published data on HGF/MET in BC were collected and analyzed.
  
  
  RESULTS
  Several evidences underline that, in early BC, MET over-expression has an independent negative prognostic significance, regardless of method used for evaluation and BC subtypes. Available data suggest that MET is a relevant target particularly in basal-like (BL) and in triple negative BC. Moreover, preclinical and retrospective data support the critical role of MET deregulation in the development of resistance to target-agents, such as anti-HER2 strategies.
  
  
  CONCLUSIONS
  MET is a promising new target in BC. Several anti-MET agents are under investigation and ongoing clinical trials will clarify its relevance in BC treatment.
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital of Livorno, Livorno, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Minuti
authors.affiliation: Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital of Livorno, Livorno, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Landi
keywords: Mesenchymal-epithelial transition (MET); basal-like (BL); breast cancer (BC); hepatocyte growth factor (HGF); triple negative