TGF-β in Human Disease

462 Pages·2013·8.49 MB·English

by  Carl-Henrik Heldin (auth.)

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. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection
with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and
executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this
publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s
location, in its current version, and permission for use must always be obtained from Springer.
Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations
are liable to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for
any errors or omissions that may be made. The publisher makes no warranty, express or implied, with
respect to the material contained herein.
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