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Hedgehog signaling activation in human cancer and its clinical implications

Author: Jingwu Xie
Publisher: New York : Springer, ©2011.
Edition/Format:   eBook : Document : EnglishView all editions and formats
Database:WorldCat
Summary:
Despite significant progress in our understanding of cancer biology, cancer continues to be the second cause of human mortality. The remarkable responses of cancer patients to inhibitors to the hedgehog signaling pathway implies a promising novel approach to treat cancer. As a result, understanding the role of hedgehog signaling in cancer is critically important for novel cancer therapeutics. The hedgehog pathway,  Read more...
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Genre/Form: Electronic books
Additional Physical Format: Print version:
Xie, Jingwu.
Hedgehog signaling activation in human cancer and its clinical implications.
Dordrecht : Springer, ©2011
Material Type: Document, Internet resource
Document Type: Internet Resource, Computer File
All Authors / Contributors: Jingwu Xie
ISBN: 9781441984357 1441984356
OCLC Number: 728101812
Description: 1 online resource (ix, 217 pages) : illustrations
Contents: Chapter 1: Overview of Hedgehog Signaling Pathway; Introduction; Hh Signal Transduction; Lipid Modification and Multimerization of Hh; Heparan Sulfate Proteoglycans Regulate Hh Signaling; Modulation of Pathway Activity by Multiple Hh-Binding Proteins; Ptc Inhibits Smo Catalytically; Regulation of Smo Trafficking and Conformation; Downstream of Smo: G Protein and Cos2/Kif 7-Ci/Gli Signaling Complex; Control of Gli Protein Degradation and Processing; Sufu: A Key Regulator of Mammalian Hh Signaling; Unresolved Questions in Mammalian Hh Signaling; References. Chapter 2: Regulation of the Hedgehog Morphogene Gradient*Introduction; Atypical Biosynthesis of Active Hh Signaling Peptide; Routing of Hh to the Plasma Membrane; Secretion and Release of Lipid-Modified Hh; Hedgehog Spreading: A Dilemma in Motion; Extracellular Gradient Formation by HSPGs; A Similar Spreading Mechanism from Flies to Mice?; Hh Uses Multiple Carriers for Its Travels; Conclusions; References; Chapter 3: Smoothened Signaling Through a G-Protein Effector Network; Introduction; Hedgehog Signal Transduction; Smoothened as a G-Protein-Coupled Receptor. SMO Signaling Through Heterotrimeric G-ProteinsA SMO-Dependent G-Protein Signaling Network; Small-Molecule Modulators of SMO; Future Directions; References; Chapter 4: Kinases and Phosphatases in Hedgehog Signaling; Phosphorylation Events in Hh Signaling; Kinases Regulating the Transcriptional Factor, Ci /Gli; Kinases Mediating the Activation of Smo in Response to Hh; Non-conserved Mechanisms of Regulation by Kinases; Phosphatases in Hh Signaling; Gradient Hh Signaling Activity Is Interpreted by Differential Phosphorylation of the Intracellular Components; References. Chapter 5: Signaling Cross-Talk of Oncogenic KRAS and Hedgehog Pathways in Pancreatic CancerIntroduction; KRAS Signaling and PDA; Cross-Talk Between KRAS and Hh Signaling in Cancer; Anticancer Therapeutics Targeting KRAS or Hh Pathway; Conclusion; References; Chapter 6: Hedgehog and Protein Kinase C Signaling; Introduction; Protein Kinase C; Functions of Different PKC Isoforms in Human Cancer; Crosstalk of HH and PKC; Crosstalk of HH and PKC in Development; Crosstalk of HH and PKC in Stem Cells; Crosstalk of HH and PKC in Human Cancer; MEK/ERK Pathway in PKC-Mediated HH Signaling; Summary.
Responsibility: Jingwu Xie, Editor.

Abstract:

Despite significant progress in our understanding of cancer biology, cancer continues to be the second cause of human mortality. The remarkable responses of cancer patients to inhibitors to the hedgehog signaling pathway implies a promising novel approach to treat cancer. As a result, understanding the role of hedgehog signaling in cancer is critically important for novel cancer therapeutics. The hedgehog pathway, initially discovered by two Nobel laureates Drs. E. Wieschaus and C. Nusslein-Volhard in Drosophila, is a major pathway regulating cell differentiation, tissue polarity, stem cell maintenance and cell proliferation. It is known by now that activation of this pathway occurs in a variety of human cancer, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. Even more exciting is the discovery and synthesis of specific signaling antagonists for the hedgehog pathway, which have significant clinical implications in novel cancer therapeutics. To provide the most up-to-date information on recent development in this exciting research area, we have invited experts in hedgehog signaling field to summarize major advances made in the last few years on hedgehog signaling mechanisms, activation of the pathway in various human cancer types, potential antagonists for hedgehog signaling inhibition and their clinical implications for human cancer treatment. Authors of the book have also highlighted current challenges in our efforts to translate the basic biology into clinic. This book provides insightful views suitable for graduate students, medical students, undergraduate students, basic and clinical scientists, cancer patients as well as the general public.

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