TGF-β in Human Disease PDF
Preview TGF-β in Human Disease
Aristidis Moustakas Keiji Miyazawa Editors TGF-β in Human Disease β TGF- in Human Disease Aristidis Moustakas (cid:129) Keiji Miyazawa Editors β TGF- in Human Disease Editors Aristidis Moustakas Keiji Miyazawa Department of Medical Biochemistry Department of Biochemistry and Microbiology Interdisciplinary Graduate and School of Medicine and Engineering Ludwig Institute for Cancer Research Ltd University of Yamanashi Uppsala University 1110 Shimokato , Chuo Box 582, SE-751 23 Yamanashi 409-3898 , Japan Uppsala, Sweden [email protected] [email protected] ISBN 978-4-431-54408-1 ISBN 978-4-431-54409-8 (eBook) DOI 10.1007/978-4-431-54409-8 Springer Tokyo Heidelberg New York Dordrecht London Library of Congress Control Number: 2013942181 © Springer Japan 2013 This work is subject to copyright. 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Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Preface More than 30 years after the discovery and purifi cation of transforming growth factor-β (TGF-β) as a secreted polypeptide from oncogenically transformed cells, this multifunctional cytokine has led major research efforts in diverse fi elds ranging from embryonic development to adult organ physiology and pathobiology of major diseases, including cancer and fi brotic, cardiovascular, and immunological diseases. Over the years, intense research efforts have resulted in a deep understanding of the signaling pathway engaged by TGF-β and many of the regulatory mechanisms of its signaling engine that allow us today to explain specifi c aspects of human disease progression based on TGF-β. Despite such major achievements, the fi eld of TGF-β signaling remains one of the most highly evolving and rapidly changing fi elds of modern biomedical science, a fact that is confi rmed by the high rate and impact of the publications produced in the fi eld. This activity underscores the current impor- tance of exploiting modern technological tools to expand and deepen the investiga- tion of TGF-β pathway perturbations in human disease. This ultimate goal of the scientifi c fi eld is feasible but far from being achieved. The present book aims to provide a comprehensive coverage of major areas of human disease where the involvement of TGF-β and the mechanistic detail of understanding are fi rmly established. Simultaneously, the book aims to highlight major gaps of knowledge and future directions of research that can benefi t human medical science. A good example is the strong potential of translational application of the TGF-β pathway in therapy for diverse human disorders. In reaching our goals, the book encompasses a broad series of topics with reference to specifi c human diseases. Owing to the vast number of human disorders where TGF-β is implicated, not all diseases are listed in the contents of this book. Furthermore, as TGF-β is a member of a large family of 33 cytokines that exhibit similarities but also unique features, the book often makes reference to some of the other growth factors of the TGF-β family but it does not comprehensively cover all of them. The core set of diseases where TGF-β action is well documented and are included in the book are cancer and cardiovascular and fi brotic disorders. Our ambition is that this book will stimulate young scientists to enter the prolifi c TGF-β fi eld and fi nd new solutions to the many open problems remaining in this v vi Preface area of study. For this reason we have made a special effort to include authoritative educational chapters that provide a good introduction to the fi eld for young doctoral students, postdocs, and clinical fellows. We believe that the book will also be a valuable reference for the pioneers and afi cionados of the fi eld, who can fi nd acces- sible and well-illustrated material for their teaching, lecturing, and other activities, via which the importance of TGF-β biology needs to be disseminated to the world of science and to the public. To meet all these goals, we as editors recruited a select group of world leaders in specifi c subjects who have delivered outstanding exam- ples of scientifi c literature. We are in debt to the meticulous work of all these authors and thank them for helping us realize our goal. Uppsala, Sweden Aristidis Moustakas Yamanashi, Japan Keiji Miyazawa Contents Part I Introduction 1 Transforming Growth Factor-β Signaling ........................................... 3 Carl-Henrik Heldin 2 TGF-β Signaling in Stem Cell Fate Determination ............................ 33 Zhongwei Li, Danny Huylebroeck, and Ye-Guang Chen 3 Emerging Roles of TGF-β Co-receptors in Human Disease .............. 59 Alison E. Meyer, Karthikeyan Mythreye, and Gerard C. Blobe Part II Cancer, Fibrosis, and Infl ammation 4 TGF-β in Cancer Stem Cells ................................................................. 93 Hiroaki Ikushima and Kohei Miyazono 5 TGF-β as Tumor Suppressor: In Vitro Mechanistic Aspects of Growth Inhibition ................................................................ 113 Laurent Bartholin, David F. Vincent, and Ulrich Valcourt 6 TGF-β as Tumor Suppressor: Lessons from Mouse Models .............. 139 Ulrich Valcourt, David F. Vincent, and Laurent Bartholin 7 The Multifunctional Roles of TGF-β in Navigating the Metastatic Cascade .......................................................................... 169 Michael K. Wendt and William P. Schiemann 8 TGF-β Signaling in Leukemogenesis ................................................... 189 Kazuhito Naka and Atsushi Hirao 9 TGF-β in Skin Cancer and Fibrosis ..................................................... 209 Gangwen Han, Zheyi Han, and Xiao-Jing Wang vii viii Contents 10 The Role of TGF-β in Cutaneous Melanoma Biology ........................ 235 Delphine Javelaud and Alain Mauviel 11 The Transforming Growth Factor-Beta (TGF- β) in Liver Fibrosis ..................................................................................... 255 Isabel Fabregat and Patricia Sancho 12 TGF-β and Inhibitory Smads in Infl ammation ................................... 279 Seong-Jin Kim and Seok Hee Park Part III Cardiovascular Diseases 13 TGF-β and Cardiovascular Disorders ................................................. 297 Laurens A. van Meeteren, Marie-José Goumans, and Peter ten Dijke 14 TGF-β Signaling in Physiological and Pathological Angiogenesis ........................................................................................... 323 Sara I. Cunha and Kristian Pietras 15 TGF-β Signaling Pathway and MicroRNAs in Cardiovascular Disease ..................................................................... 349 Nisha Marathe and Akiko Hata Part IV Other Diseases 16 TGF-β and Genetic Skeletal Diseases .................................................. 371 Shiro Ikegawa, Mitsuko Nakashima, and Naomichi Matsumoto 17 TGF-β in Brain Disorders ..................................................................... 391 Kerstin Krieglstein 18 TGF-β and Metabolic Homeostasis ...................................................... 413 Grace Bennett and Sushil G. Rane Part V Disease Prognosis and Therapy 19 Targeting Pro-Angiogenic TGF-β Signaling in the Tumor Microenvironment ................................................................................. 435 Kristian Pietras and Sara I. Cunha Index ................................................................................................................ 459 Part I Introduction
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