Cellular Senescence and Tumor Suppression

274 Pages·2010·4.805 MB·English

by  Laura Gardano, Lea Harrington (auth.), Peter D. Adams, John M. Sedivy (eds.)

Cellular Senescence and Tumor Suppression
Peter D. Adams John M. Sedivy
●
Editors
Cellular Senescence
and Tumor Suppression
Editors
Peter D. Adams John M. Sedivy
CRUK Beatson Labs Department of Molecular Biology
University of Glasgow Cell Biology and Biochemistry
Garscube Estate Brown University
Switchback Road Providence, RI 02912
Glasgow, G20 8PU USA
UK [email protected]
[email protected]
ISBN 978-1-4419-1074-5 e-ISBN 978-1-4419-1075-2
DOI 10.1007/978-1-4419-1075-2
Springer New York Dordrecht Heidelberg London
Library of Congress Control Number: 2009933096
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Contents
Introduction ..................................................................................................... ix
John M. Sedivy
Section 1 Senescence Signals
1 Telomere Biology and Biochemistry ........................................................ 3
Laura Gardano and Lea Harrington
2 Role of RecQ Helicases in Nuclear DNA Repair and Telomere
Maintenance .............................................................................................. 45
Avik Ghosh, Yie Liu, and Vilhelm A. Bohr
3 Oncogene-Induced Senescence (OIS) as a Cellular Response
to Oncogenic Stresses ................................................................................ 63
Véronique Bourdeau and Gerardo Ferbeyre
4 Stress-Induced Senescence ....................................................................... 85
Peter J. Hornsby
Section 2 The Senescent Phenotype
5 The Secretome of Senescent Cells ............................................................ 109
Gowrishankar Banumathy and Peter D. Adams
6 Chromatin Structure in Senescent Cells ................................................. 125
Hunter W. Richards and Estela E. Medrano
7 A Comparison of Senescence in Mouse and Human Cells .................... 175
Vera Gorbunova and Andrei Seluanov
v
vi Contents
Section 3 The Physiological Consequences of Senescence
8 Replicative Senescence as an Intrinsic Tumor-Suppressor
Mechanism ............................................................................................... 201
Sandy Chang
9 Telomere Dysfunction and Senescence in Stem Cell
and Tissues Aging ................................................................................... 219
Kodandaramireddy Nalapareddy and K. Lenhard Rudolph
10 Mining Cellular Senescence for Drug Targets ...................................... 235
Alan E. Bilsland and W. Nicol Keith
Index ................................................................................................................. 267
Contributors
Peter D. Adams
CRUK Beatson Labs, University of Glasgow, Garscube Estate,
Glasgow G20 8PU, UK
[email protected]
Gowrishankar Banumathy
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
[email protected]
Alan E. Bilsland
Centre for Oncology and Applied Pharmacology, University of Glasgow, Cancer
Research UK Beatson Laboratories, Garscube Estate, Switchback Road,
Bearsden, Glasgow G61 1BD, UK
[email protected]
Vilhelm A. Bohr
Laboratory of Molecular Gerontology, 5600 Nathan Shock Drive,
Baltimore, MD 21224-6825, USA
[email protected]
Véronique Bourdeau
Département de Biochimie, Université de Montréal, C.P. 6128,
Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
[email protected]
Sandy Chang, M.D., Ph.D.
Assistant Professor, Unit 1006, U.T.M.D. Anderson Cancer Center,
Department of Molecular Genetics, 1515 Holcombe Boulevard, Houston,
TX 77030, USA
[email protected]
Gerardo Ferbeyre
Département de Biochimie, Université de Montréal, C.P. 6128,
Succ. Centre-Ville, Montréal, QC, Canada H3C 3J7
[email protected]
vii
viii Contributors
Laura Gardano
Wellcome Trust Centre for Cell Biology, University of Edinburgh,
Michael Swann Building, Kings Buildings, Mayfield Road,
EDINBURGH EH9 3JR
[email protected]
Avik Ghosh
Laboratory of Molecular Gerontology, 5600 Nathan Shock Drive, Baltimore,
MD 21224-6825, USA
[email protected]
Vera Gorbunova
Department of Biology, University of Rochester, 213 Hutchison Hall,
River Campus, Box 270211, Rochester, NY 14627-0211, USA
[email protected]
Lea Harrington
Wellcome Trust Centre for Cell Biology, University of Edinburgh,
Michael Swann Building, Kings Buildings, Mayfield Road,
EDINBURGH EH9 3JR
[email protected]
Peter Hornsby
Professor, Department of Physiology, Sam and Ann Barshop Inst. for Longevity
and Aging Studies, University of Texas Health Science Center, 15355 Lambda
Drive, STCBM Bldg., San Antonio, TX 78245, USA
[email protected]
W. Nicol Keith
Cancer Research UK Beatson Laboratories, Centre for Oncology
and Applied Pharmacology, University of Glasgow, Garscube Estate,
Switchback Road, Bearsden, Glasgow G61 1BD, UK
[email protected]
Yie Liu
Laboratory of Molecular Gerontology, 5600 Nathan Shock Drive,
Baltimore, MD 21224-6825, USA
[email protected]
Estela E. Medrano
Department of Molecular and Cellular Biology, Baylor College
of Medicine, One Baylor Plaza, Houston, TX 77030, USA
[email protected]
Kodandaramireddy Nalapareddy
Institute of Molecular Medicine and Max-Planck-Research-Group
on Stem Cell Aging, Albert-Einstein-Allee 11, 89081 Ulm, Germany
[email protected]
Contributors ix
Hunter W. Richards
Huffington Center on Aging, Baylor College of Medicine, Houston,
TX 77030, USA
K.Lenhard Rudolph
Institute of Molecular Medicine and Max-Planck-Research-Group
on Stem Cell Aging, Albert-Einstein-Allee 11, 89081 Ulm, Germany
[email protected]
Andrei Seluanov
Department of Biology, University of Rochester, 213 Hutchison Hall,
River Campus, Box 270211, Rochester, NY 14627-0211, USA
[email protected]
Introduction
John M. Sedivy
Age-related diseases, such as malignant neoplasms, are among the leading causes
of death and disability in modern societies. Two fundamental cellular aging pro-
cesses have been described. One is chronological aging, and is the consequence of
time-dependent changes that result from the breakdown of the balance between
biosynthesis, repair and turnover. Chronological aging – an important component
of which is the accumulation of damaged or otherwise dysfunctional macromole-
cules – is of paramount importance in terminally differentiated cells. Replicative
aging, on the other hand, reflects the inability of a cell (and thus its lineage) to sup-
port the ongoing rounds of cell division. It is thus believed to be of major impor-
tance in complex metazoan organisms, such as mammals, whose adult bodies
depend on the extensive tissue turnover. Cell division is however a double-edged
sword that needs to be tightly regulated: it counteracts chronological aging (by the
simple dilution of damaged macromolecules) and leads to the genesis of new func-
tional cells, while excessive replication places the organism at risk of malignant
transformation.
Replicative cellular aging, termed cellular senescence, was discovered in 1961
and described by Leonard Hayflick as an irreversible growth arrest triggered by the
accumulation of a discrete number of cell divisions. The great majority of normal
cell types from all vertebrate species display this response. The underlying cause of
senescence due to replicative exhaustion is telomere shortening, a molecular count-
ing mechanism that monitors elapsed cell divisions. It is now evident, however, that
what had been classically described as replicative senescence is in fact a collection
of interrelated states that can be triggered by distinct intrinsic and extrinsic stimuli.
Although dysfunctional telomeres are sufficient to trigger senescence, and in some
cases are the primary cause, it is now apparent that many types of stress, including
ionizing and ultraviolet irradiation, reactive oxygen species, pharmacological
agents that modify DNA or chromatin, nutrient imbalances, and even culture condi-
tions can trigger a cellular senescence response.
J.M. Sedivy
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence,
R1 02912, USA
e-mail: [email protected]
xi