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Met Activation and Carcinogenesis

  • Nariyoshi Shinomiya
  • Qian Xie
  • George F. Vande Woude
Chapter
Part of the Current Human Cell Research and Applications book series (CHCRA)

Abstract

MET is a tyrosine kinase receptor that transduces intracellular signaling to activate the MAPK, PI3K-Akt, and cadherin pathways (among others). In cancer cells, MET is activated upon stimulation by its only ligand, hepatocyte growth factor/scatter factor (HGF/SF), or becomes active due to mutations or amplifications that produce constitutive activation of the MET kinase. The biological consequences of HGF/SF-MET signaling include cell proliferation, cell cycle progression, increased cell motility and invasive activity, and degradation of extracellular matrices, which can lead to oncogenesis. Aberrant MET signaling contributes to the carcinogenesis of hereditary cancers and also plays a major role in the spread of cancer cells; such signaling indicates a poor prognosis for cancer patients. Genetically engineered mouse models are important tools for studying the spontaneous development of tumors mediated by HGF/SF-MET signaling. Such tumors include carcinomas, sarcomas, and lymphomas, demonstrating the breadth of MET signaling as driving force of cancer. In this chapter, we will discuss the role of HGF/SF-MET signaling in carcinogenesis and the animal models used in developing therapeutic strategies that target the HGF/SF-MET signaling pathways.

Keywords

Met/MET HGF/SF Carcinogenesis Epithelial–mesenchymal transition (E–MT) Dysregulation Constitutive activation Genetically engineered mouse models 

Abbreviations

MET

human MET

Met

mouse Met

Notes

Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research, Japan Society for the Promotion of Science (to N. S.; #15H04315), by the Stephen M. Coffman Charitable Trust and ETSU start-up funds (to Q. X.), and by the generosity of the Jay & Betty Van Andel Foundation (to G. V. W.). We are very grateful to David Nadziejka (Van Andel Research Institute) for technical editing of the manuscript.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Nariyoshi Shinomiya
    • 1
  • Qian Xie
    • 2
  • George F. Vande Woude
    • 3
  1. 1.Department of Integrative Physiology and Bio-Nano MedicineNational Defense Medical CollegeTokorozawaJapan
  2. 2.Department of Biomedical SciencesCenter of Excellence for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State UniversityJohnsonUSA
  3. 3.Distinguished Scientific Fellow, EmeritusVan Andel Research InstituteGrand RapidsUSA

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