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Discoidin Domain Receptors in Health and Disease

  • Rafael Fridman
  • Paul H. Huang

Table of contents

  1. Front Matter
    Pages i-xiv
  2. Discoidin Domain Receptor Biology and Roles in Physiology

    1. Front Matter
      Pages 1-1
    2. Gunjan Agarwal
      Pages 23-56
    3. Noritaka Nishida, Ichio Shimada
      Pages 57-67
    4. Kiyoshi Kano, Ken Takeshi Kusakabe, Yasuo Kiso
      Pages 69-86
    5. Thomas Unsoeld, Jesse Taylor, Harald Hutter
      Pages 87-105
  3. Discoidin Domain Receptors in Cancer

    1. Front Matter
      Pages 107-107
    2. Gregory D. Longmore, Whitney R. Grither
      Pages 109-117
    3. Sandamali A. Ekanayaka, Celina G. Kleer, Aliccia Bollig-Fischer, Rodrigo Fernandez-Valdivia, Rafael Fridman
      Pages 119-144
    4. Yingtao Zhang, Agnes Malysa, Gerold Bepler
      Pages 145-154
    5. Marta Marco, Paul R. Gill
      Pages 155-179
    6. Leo K. Iwai, Leo S. Payne, Dina Allam, Paul H. Huang
      Pages 201-216
    7. Pedro A. Ruiz-Castro, Duncan Shaw, Gabor Jarai
      Pages 217-238
    8. Yi-Chun Yeh, Ming-Jer Tang
      Pages 239-258
  4. Discoidin Domain Receptors in Other Pathologies

    1. Front Matter
      Pages 259-259
    2. Lin Xu, Peter L. Lee, Yefu Li
      Pages 261-279
    3. Christos Chatziantoniou, Aude Dorison, Jean-Claude Dussaule
      Pages 281-291
    4. Elvira Olaso, Joana Marquez, Aitor Benedicto, Iker Badiola, Beatriz Arteta
      Pages 293-313
    5. Michelle P. Bendeck
      Pages 315-330
    6. David E. Justus, Adam Hoffman, Ekaterina Mironova, Alexander Hartman, Jack G. Goldsmith, Jay D. Potts et al.
      Pages 331-347
  5. Back Matter
    Pages 349-355

About this book

Introduction

The interactions of cells with their surrounding extracellular matrix (ECM) plays a pivotal role in driving normal cell behavior, from development to tissue differentiation and function. At the cellular level, organ homeostasis depends on a productive communication between cells and ECM, which eventually leads to the normal phenotypic repertoire that characterize each cell type in the organism.  A failure to establish these normal interactions and to interpret the cues emanating from the ECM is one of the major causes in abnormal development and the pathogenesis of multiple diseases. To recognize and act upon the biophysical signals that are generated by the cross talk between cells and ECM, the cells developed specific receptors, among them a unique set of receptor tyrosine kinases (RTKs), known as the Discoidin Domain Receptors (DDRs). The DDRs are the only RTKs that specifically bind to and are activated by collagen, a major protein component of the ECM. Hence, the DDRs are part of the signaling networks that translate information from the ECM, and thus they are key regulators of cell-matrix interactions. Under physiological conditions, DDRs control cell and tissue homeostasis by acting on collagen sensors; transducing signals that regulate cell polarity, tissue morphogenesis, cell differentiation, and collagen deposition. DDRs play a key role in diseases that are characterized by dysfunction of the stromal component, which lead to abnormal collagen deposition and the resulting fibrotic response that disrupt normal organ function in disease of the cardiovascular system, lungs and kidneys, just to mention a few. In cancer, DDRs are hijacked by tumor and stromal cells to disrupt normal cell-collagen communication and initiate pro-oncogenic programs. Importantly, several cancer types exhibit DDR mutations, which are thought to alter receptor function, and contribute to cancer progression. Therefore, the strong causative association between altered RTK function and disease it is been translated today in the development of specific tyrosine kinase inhibitors targeting DDRs for various disease conditions. In spite of the accumulating evidence highlighting the importance of DDRs in health and diseases, there is still much to learn about these unique RTKs, as of today there is a lack in the medical literature of a book dedicated solely to DDRs. This is the first comprehensive volume dedicated to DDRs, which will fill a gap in the field and serve those interested in the scientific community to learn more about these important receptors in health and disease.

Keywords

cancer migration cell signaling collagen extracellular matrix receptor tyrosine kinases

Editors and affiliations

  • Rafael Fridman
    • 1
  • Paul H. Huang
    • 2
  1. 1.Department of PathologyWayne State University School of Medicine and Karmanos Cancer InstituteDetroitUSA
  2. 2.Division of Cancer BiologyThe Institute of Cancer ResearchLondonUnited Kingdom

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