Ann Transl Med. 2015 Aug;3(13):181. doi: 10.3978/j.issn.2305-5839.2015.06.22.
MET deregulation in breast cancer.
Annals of translational medicine
Gabriele Minuti, Lorenza Landi
Affiliations
Affiliations
- Department of Medical Oncology, Istituto Toscano Tumori, Civil Hospital of Livorno, Livorno, Italy.
PMID: 26366398
PMCID: PMC4543340 DOI: 10.3978/j.issn.2305-5839.2015.06.22
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.
Keywords: Mesenchymal-epithelial transition (MET); basal-like (BL); breast cancer (BC); hepatocyte growth factor (HGF); triple negative
References
- Cancer. 2014 Jan 15;120(2):163-71 - PubMed
- Cancer Res. 2003 Mar 1;63(5):1101-5 - PubMed
- Br J Cancer. 2013 Mar 19;108(5):1100-5 - PubMed
- Nature. 1995 Feb 23;373(6516):702-5 - PubMed
- Clin Cancer Res. 2014 Jul 1;20(13):3361-3 - PubMed
- Int J Cancer. 2014 May 15;134(10):2424-36 - PubMed
- Oncogene. 2006 Apr 6;25(15):2273-84 - PubMed
- Oncotarget. 2014 Sep 30;5(18):8147-60 - PubMed
- Clin Cancer Res. 2012 Apr 15;18(8):2269-77 - PubMed
- Cancer Res. 1994 Apr 1;54(7):1630-3 - PubMed
- Clin Cancer Res. 2008 Apr 1;14(7):1938-46 - PubMed
- Diagn Pathol. 2015 Jun 06;10:62 - PubMed
- Tumour Biol. 2006;27(3):115-21 - PubMed
- Hum Pathol. 2007 Jun;38(6):830-41 - PubMed
- Mol Cell Proteomics. 2008 Aug;7(8):1420-33 - PubMed
- Lung Cancer. 1998 Apr;20(1):1-16 - PubMed
- Pharmacol Ther. 2014 Sep;143(3):337-49 - PubMed
- Histopathology. 2007 Jul;51(1):54-62 - PubMed
- Mod Pathol. 2011 Feb;24(2):157-67 - PubMed
- Br J Cancer. 2012 Aug 21;107(5):793-9 - PubMed
- Breast Cancer Res. 2010;12(4):208 - PubMed
- Adv Exp Med Biol. 2008;617:511-7 - PubMed
- Int J Cancer. 1999 Sep 9;82(6):908-10 - PubMed
- Oncogene. 2006 Jan 19;25(3):409-18 - PubMed
- Mol Cancer Res. 2013 Sep;11(9):1112-21 - PubMed
- Anticancer Res. 2013 Nov;33(11):5179-86 - PubMed
- Science. 1991 Feb 15;251(4995):802-4 - PubMed
- Nat Rev Cancer. 2006 Aug;6(8):637-45 - PubMed
- J Clin Oncol. 2015 Jan 20;33(3):244-50 - PubMed
- J Cell Biol. 1992 Nov;119(3):629-41 - PubMed
- J Clin Oncol. 2009 Apr 1;27(10):1667-74 - PubMed
- Science. 2007 May 18;316(5827):1039-43 - PubMed
- Cancer Discov. 2013 Jun;3(6):658-73 - PubMed
- Lab Invest. 1998 Sep;78(9):1143-53 - PubMed
- Breast Cancer Res. 2009;11(2):402 - PubMed
- Cancer Res. 2008 Mar 1;68(5):1471-7 - PubMed
- N Engl J Med. 2001 Mar 15;344(11):783-92 - PubMed
- J Clin Oncol. 2011 Dec 20;29(36):4789-95 - PubMed
- Cancer. 1999 Dec 1;86(11):2259-65 - PubMed
- Int J Cancer. 2005 Feb 10;113(4):678-82 - PubMed
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