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El. knyga: Notch Signaling in Embryology and Cancer

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This comprehensive assessment of our present knowledge of the role of notch signaling in embryology and cancer analyzes a range of topics from the latest findings in cellular and molecular pathology to new concepts for prophylaxis and treatment of cancer.



The goal of this volume is to comprehensively cover a highly readable overview on our present knowledge of the role of Notch signalling for embryology and cancer, with a focus on new findings in molecular biology. Topics that are discussed in-depth by leading researchers and clinicians range from the newest findings in cellular and molecular pathology to new concepts for prophylaxis and treatment of cancer. Experts in the field as well as scientists and health care professionals not intimately involved in these specialized areas are provided with the most significant and timely information related to these topics. It is the aim of this book to summarize essential up-to-date information for every clinician or scientist interested in the role of Notch signalling in embryology and cancer. We hope that this volume will be adopted as the standard text in this area of science and will stimulate new interest in the role of Notch signalling for embryology and cancer. We further hope that this compendium will serve as both a source for current researchers and a guide to stimulate and assist those in related disciplines to enter this exciting field of research.
1 The Molecular Basis of Notch Signaling: A Brief Overview
1(14)
Sang-Mo Kwon
Cantas Alev
Sang-Hun Lee
Takayuki Asahara
Abstract
1(1)
Introduction
1(1)
Basic Mechanisms of Notch Signaling Pathways
2(2)
Modulation of Notch Signal Transduction
4(1)
Notch Signaling in Vascular Development
5(1)
Notch Signaling in Cancer Development
6(3)
Notch in Solid Tumors
9(1)
Notch Signaling in Embryonic Development
9(1)
Origins of Roles for Notch Signaling in Early Embryogenesis
10(1)
Notch Signaling is Often Involved in Mesoderm Formation
11(1)
Conclusion
11(4)
2 The Role of Adams in Notch Signaling
15(22)
Arjan J. Groot
Marc A. Vooijs
Abstract
15(1)
Introduction
15(2)
Notch Signaling
17(1)
Notch Proteolysis Site-1 (S1, Furin, Serine Protease)
17(1)
Site-3 (S3, Presenilin, Aspartyl Protease)
18(1)
The Adam Family of Proteases
19(4)
Notch Ligand Cleavage by Adams
23(4)
Location of S2 Cleavage
27(1)
Targeting S2 Proteolysis in Cancer
28(2)
Conclusion
30(7)
3 Metabolism and Transportation Pathways of GDP-Fucose That are Required for the O-fucosylation of Notch
37(10)
Tomoko Yamakawa
Tomonori Ayukawa
Kenji Matsuno
Abstract
37(1)
Introduction
37(1)
Proper Structure of its Extracellular Domain is Crucial for the Activation of Notch
38(1)
Modifications of O-Linked Glycans in the EGF-Like Repeats of Notch
38(2)
The Monosaccharide O-Fucose Modification on the EGF-Like Repeats of Notch Does Not Have a Major Role in Notch Signaling
40(1)
Metabollc Pathway for the O-Fucose Modification of Notch EGF-Like Repeats
41(2)
Intracellular Transportation of GDP-Fucose is Crucial for the O-Fucosylation of Notch EGF-Like Repeats
43(1)
A Reduction in Notch Signaling Activity May Account for the Pathology of CDG IIc
44(1)
Mechanisms Required for the Intracellular Supply of GDP-Fucose for the O-Fucosylation of the Notch EGF-Like Repeats
44(1)
Conclusion
45(2)
4 Notch Signaling and the Generation of Cell Diversity in Drosophila Neuroblast Lineages
47(14)
Gerald Udolph
Abstract
47(1)
Introduction
47(1)
Notch is Required for Lateral Inhibition During the Phase of Neural Stem Cell Generation
48(1)
Asymmetric Cell Division as a Mechanism to Generate Cell Diversity in Neuroblast Lineages
49(1)
Function of Notch in Binary Cell Fate Specification in the Drosophila Nervous System
50(2)
Notch Function in Cell Fate Specification in the Embryonic NB7-3 Lineage
52(1)
Notch Function During Larval Neurogenesis
52(3)
Down-Stream Notch Targets/Effectors
55(1)
Conclusion
56(5)
5 Nepro: A Novel Notch Effector for Maintenance of Neural Progenitor Cells in the Neocortex
61(10)
Tetsuichiro Saito
Abstract
61(1)
Introduction
61(1)
The Notch Pathway is Essential for Maintenance of NPCs
62(1)
Identification of Nepro
63(1)
Nepro Inhibits Neuronal Differentiation and is Necessary for the Maintenance of NPCs
64(1)
Nepro is in Parallel with Hes, Downstream of Notch
64(1)
Nepro is an Essential Effector for the Notch Pathway
64(3)
Discussion
67(2)
Conclusion
69(2)
6 Notch Signaling and Development of the Hematopoietic System
71(18)
Ashley R. Sandy
Morgan Jones
Ivan Maillard
Abstract
71(1)
Introduction
71(1)
Overview of Notch Signaling
72(3)
Notch and Emergence of Definitive Hematopoietic Stem Cells
75(3)
Notch and Maintenance of Hematopoietic Stem Cells
78(3)
Notch and T-Cell Development
81(1)
Other Functions of Notch in Hematopoiesis
82(1)
Conclusion
83(6)
7 Notch Signaling in Lung Development and Disease
89(10)
Keli Xu
Nadeem Moghal
Sean E. Egan
Abstract
89(1)
Introduction
89(1)
Notch Promotes Proximal Cell Fates in Early Lung Development
90(2)
Notch Coordinates Alveolar Development
92(1)
The Role of Notch in Repair and Disease of the Adult Lung
93(1)
Notch and Lung Cancer
94(2)
Conclusion
96(3)
8 The Role of Notch Signaling in Kidney Development and Disease
99(15)
Hila Barak
Kameswaran Surendran
Scott C. Boyle
Abstract
99(1)
Introduction
99(2)
Notch Signaling in Pronephros Development
101(2)
Notch Signaling in Metanephros Development
103(6)
Notch Signaling in Kidney Diseases and Renal Epithelial Cancers
109(1)
Conclusion
110(4)
9 Notch Signaling and the Developing Skeleton
114(17)
Timothy J. Mead
Katherine E. Yutzey
Abstract
114(1)
Introduction
114(10)
Notch Pathway Associated Skeletal Disorders
124(2)
Conclusion
126(5)
10 Notch Signaling and the Developing Skin Epidermis
131(11)
Daniela Massi
John Panelos
Abstract
131(1)
Introduction
131(1)
Notch Signaling
132(1)
Localization of Notch Receptors and Ligands in Epidermis
133(1)
Growth Arrest and Adhesion
133(1)
Notch and Terminal Differentiation
134(1)
Deletion or Activation of Notch Pathway Components
135(1)
Cross-Talks with Other Pathways
136(2)
Conclusion
138(4)
11 Notch Signaling and the Developing Hair Follicle
142(19)
Genevieve Aubin-Houzelstein
Abstract
142(1)
Introduction
142(1)
Development and Structure of the Hair Follicle
143(4)
Expression of Members of the Notch Pathway in the Hair Follicle
147(1)
No Essential Role for Notch in the Initial Steps of Embryonic Hair Follicle Development
148(3)
Notch and the Maintenance of Cellular Identity within the Hair Follicle
151(3)
Notch and the Regulation of Cell Fate in Hair Follicles
154(2)
Additional Roles for Notch in Hair Follicles
156(2)
Conclusion
158(3)
12 Notch Signaling and the Developing Inner Ear
161(13)
Junko Murata
Katsuhisa Ikeda
Hideyuki Okano
Abstract
161(1)
Introduction: Structure and Development of Mammalian Inner Ear
161(2)
Multiple Roles of Notch Signaling Pathway During Inner Ear Development
163(6)
Notch Signaling Pathway and the Inner Ear Regeneration
169(1)
Conclusion
170(4)
13 Notch Signaling in Cancer Stem Cells
174(12)
Jialiang Wang
Bruce A. Sullenger
Jeremy N. Rich
Abstract
174(1)
Introduction
174(1)
The Cancer Stem Cell Model
175(1)
Clinical Implications of Cancer Stem Cells
176(1)
Cancer Stem Cells and Chemoresistance
177(1)
Cancer Stem Cells and Radioresistance
178(1)
Notch Signaling in Cancer Stem Cells
179(1)
Notch Protects Cancer Stem Cells From Radiation
180(1)
Conclusion
181(5)
14 Notch Signaling Pathway and Cancer Metastasis
186(13)
Yi-Yang Hu
Min-hua Zheng
Rui Zhang
Ying-Min Liang
Hua Han
Abstract
186(1)
Introduction
186(1)
Critical Cellular and Molecular Events in Cancer Metastasis
187(2)
The Notch Signaling Pathway
189(1)
Notch Signaling Pathway and Cancer Metastasis
190(2)
The Mechanisms of Notch Function on Cancer Metastasis
192(2)
Conclusion
194(5)
15 Notch, Apoptosis and Cancer
199(11)
Thao P. Dang
Abstract
199(1)
Introduction
199(2)
p53 Pathway
201(1)
NF-kB Pathway and Notch in Apoptosis
202(2)
PI3K-Akt Pathway
204(1)
Notch and the Major Apoptotic Pathways
205(1)
Conclusion
206(4)
16 Ligand-Dependent Notch Signaling in Vascular Formation
210(13)
Tsutomu Kume
Abstract
210(1)
Introduction
210(1)
Basic Mechanisms of the Notch Receptor Ligand-Signaling Pathway
211(1)
Notch Receptor and Ligand Expression in Blood Vessels
212(1)
Notch1, Notch4 and the Ligands Dll1 and Dll4 During Arterial Specification and Maintenance
213(4)
Notch3, Jagged1 and Dll1 During Smooth-Muscle Differentiation and Maturation
217(1)
Dll4 and Jagged1 in Tip- and Stalk-Cell Specification During Sprouting Angiogenesis
217(1)
Notch Ligands in Pathological Angiogenesis
218(1)
Notch Signaling in Peripheral Ischemia
218(1)
Conclusion
219(4)
17 Notch and the p53 Clan of Transcription Factors
223(18)
Klaus Roemer
Abstract
223(1)
Introduction
223(1)
Notch
224(1)
The p53 Clan
225(3)
Crosstalk of Notch with the p53 Clan in Development, Differentiation and Homeostasis
228(3)
Crosstalk of Notch with the p53 Clan in Cancer and Other Diseases
231(3)
Conclusion
234(7)
18 Notch Signaling and Breast Cancer
241(17)
Michael Reedijk
Abstract
241(1)
Introduction
241(1)
Evidence for Oncogenic Notch in Carcinoma of the Breast
242(1)
Mechanisms of Notch Activation in Breast Cancer
243(1)
Mechanisms of Notch-Induced Transformation
244(4)
Notch Target Genes and Tumor Progression
248(2)
Notch Inhibition in the Clinical Setting
250(3)
Conclusion
253(5)
19 Notch Signaling and Malignant Melanoma
258(7)
Cornelia S.L. Muller
Abstract
258(1)
Introduction
258(2)
Preface of Notch Signaling
260(1)
Notch and Melanocytes
260(2)
Notch Signaling and Malignant Melanomas
262(1)
Conclusion
263(2)
20 Notch-Signaling and Nonmelanoma Skin Cancer: An Ancient Friend, Revisited
265(7)
Jorg Reichrath
Sandra Reichrath
Abstract
265(1)
Introduction
265(1)
Notch Signaling
266(1)
The Notch Signaling Pathway in the Skin
266(2)
Notch Signaling and Nonmelanoma Skin Cancer
268(1)
The Effects of Notch1 Deletion on Multistage Events in Skin Carcinogenesis
269(1)
Conclusion
270(2)
21 Notch Signaling and Intestinal Cancer
272(17)
Sandra Guilmeau
Abstract
272(1)
Introduction: Adult Intestinal and Colonic Cell Homeostasis
272(3)
The Basics of Notch Signaling
275(2)
Distribution of Notch Signaling Components in the Gut
277(1)
Notch and Gut Cell Fate Determination
277(2)
Notch-Mediated Lateral Inhibition Process
279(2)
Links Between Notch and Colorectal Cancer: What Do We Know?
281(2)
Regulation of Angiogenesis by the Notch Pathway
283(1)
Interaction Between Notch and Wnt Signaling Pathways
283(2)
Regulation of Notch Signaling in Chemoprevention and Chemotherapy
285(1)
Conclusion
286(3)
22 Notch Signaling and Brain Tumors
289(16)
Marie-Therese Stockhausen
Karina Kristoffersen
Hans Skovgaard Poulsen
Abstract
289(1)
Introduction to Brain Tumors
289(2)
Expression of Notch Pathway Components and Glioma Grade
291(1)
Functional Significance of Notch Signaling in Gliomas
291(1)
Notch Signaling in Medulloblastoma---Oncogene Versus Tumor Suppressor
292(1)
Brain Cancer Stem Cells in Gliomas and Medulloblastomas
292(1)
Expression of Notch Pathway Components in bCSC
293(2)
Functional Role of Notch Signaling in bCSC
295(1)
Notch Signaling and Intracellular Cross-Talk in Gliomas
296(2)
Notch Signaling Cross-Talk in Medulloblastoma
298(1)
Hypoxia and Angiogenesis---Mediators of Notch Signaling in Gliomas
298(1)
Notch as a Therapeutic Target in Brain Tumors
299(1)
Conclusion
300(5)
23 Notch Inhibition as a Promising New Approach to Cancer Therapy
305(16)
Benjamin Purow
Abstract
305(1)
Introduction: Background of the Notch Pathway in Cancer
305(1)
Rationale for Notch Inhibition
306(2)
Potential Risks of Notch Inhibition
308(1)
Strategies for Notch Inhibition
309(6)
Conclusion
315(6)
Index 321
JÖRG REICHRATH is Professor for Dermatology and Deputy Director of the Clinic for Dermatology, Allergology and Venerology at the Saarland University Hospital in Homburg/Saar, Germany. Main research interests include photobiology, dermato-endocrinology and dermato-oncology. He is a member of numerous national and international scientific organizations, including the German Dermatological Society (DDG), the Deutsche Krebsgesellschaft (DKG), the German Dermatologic Cooperative Oncology Group (DeCOG), and the European Society of Dermatological Research (ESDR). He has been awarded numerous prices including the Arnold-Rikli-price 2006. Jörg Reichrath received his academic degrees (Dr. med., venia legendi) from the Saarland University, Germany.

SANDRA REICHRATH is working as a scientist at the Clinic for Internal Medicine of the Saarland University Hospital in Homburg/Saar, Germany. Main research interests include Notch signalling in glioblastoma and skin tumors. She received her academic degrees from the Faculty of Biology of the Albert-Ludwig-University, Freiburg, Germany.
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