Wnt Signaling


Book Description

Wnt proteins are signaling molecules that play critical roles during embryonic development and in the regeneration of adult tissues. They bind to Frizzled and LRP family receptors on the cell surface, triggering a series of events that cause ?-catenin to enter the nucleus and activate transcription factors that control cell fate and cell proliferation. Mutations in components of the Wnt pathway lead to developmental defects and are common in cancer. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of canonical Wnt signaling, as well as ?-catenin-independent Wnt signaling and cross-talk with other pathways. The contributors examine the numerous Wnt ligands; their production, secretion, and interactions with components of the extracellular environment; and details of the downstream signaling pathways that mediate the effects of Wnt proteins on cells. The roles of Wnt signaling in stem cell self-renewal, cell polarity, body-axis specification, wound healing, and other aspects of normal development and physiology are also covered. This volume includes discussion of Wnt signaling in cancer, skeletal defects, neurological disorders, and other human disease states. Thus, it is an indispensable reference for cell and developmental biologists as well as those, especially in the fields of stem cell biology and regenerative medicine, who are interested in targeting the Wnt pathway for therapeutic purposes.




Wnt Signaling in Development and Disease


Book Description

Wnt signaling in Development and Disease: Molecular Mechanisms and Biological Functions reviews the core topics in Wnt signaling, from molecular pathway mechanisms to its role in embryogenesis, adult tissue homeostasis, and chronic disease. Written by a team of expert reviewers, the book provides clear and concise coverage of the core foundations of Wnt signaling before advancing to discussion of cutting-edge scientific research. Focused on the biological insights and current scientific questions of Wnt signaling, this book will be a comprehensive and definitive resource for a wide range of researchers and students in cell signaling, cell physiology, developmental biology, and biomedical engineering, as well as anyone interested in learning more about this important and complex protein network. • A definitive source of information on Wnt signaling and its role in development and disease, written by leaders in the field. • Explores the role of Wnt signaling in chronic disease such as melanoma, colorectal cancer, dementia, and psychiatric diseases • Reviews the complex processes of signal integration and regulation • Features broad discussion of Wnt signaling biology as well as detailed discussion of the pathway’s role in diseases and potential clinical applications.




Pharmacology of the WNT Signaling System


Book Description

This book reflects the state of the art of our understanding of the WNT signaling system, which comprises a network of signaling pathways initiated by the secreted WNT lipoglycoproteins, which are crucial for embryonal development, stem cell regulation, tissue homeostasis and repair. Dysfunction of this evolutionarily conserved signaling system leads to many diseases including developmental disorders, diverse forms of cancer, fibrosis, neurodegenerative disease and many more. The WNT signaling system is built upon 19 mammalian, secreted WNT lipoglycoproteins that interact with a plethora of distinct receptors, such as the G protein-coupled receptors called Frizzleds (FZD1-10), LDL receptor-like proteins (LRP5/6), receptor tyrosine kinases (ROR1, 2, RYK and PTK7). In addition, WNT pathways are tightly regulated by many secreted and cell-intrinsic negative regulators, such as soluble FZD-related proteins (SFRPs), Dickkopfs (DKKs), WNT-inhibitory proteins, TIKI, RNF43 and more. Understanding the basic mechanism in terms of receptor-ligand interaction, receptor selectivity, signal initiation and desensitization remain poorly understood, even though substantial advances have been made the recent years. Due to the involvement of the WNT signaling system in human disease, it appears obvious to target diverse branches pharmacologically and therapeutically. However, given the complexity of the system and its importance for stem cell regulation and tissue maintenance, therapy comes with obvious risks for severe side effects. The field is addressing the challenge to identify suitable targets and selective compounds for therapy allowing disease-selective therapeutic effects and balancing unwanted side effects. This book summarizes the current understanding of the basic and applied pharmacology in the WNT signaling system and bridges disciplines such as pharmacology, physiology, neurosciences, oncology and drug development.







Sammy, I Love You


Book Description

An inspirational true story of devotion, courage and determination in the face of great tragedy - a story that will touch your heart.







Targeting the Wnt Pathway in Cancer


Book Description

Inappropriate activation of the Wnt signaling pathway is observed in many human cancers and is sufficient to drive tumor initiation and progression in numerous contexts. Multiple mechanisms, such as overexpression of Wnt ligands, inactivation of the APC and Axin tumor suppressors, and mutation of -catenin, are responsible for pathway activation in tumor cells. The development of potent Wnt pathway antagonists for therapeutic use has been a major effort for investigators in both academia and industry in recent years. This book will provide an overview of the Wnt pathway as a therapeutic target for cancer, and discuss the preclinical development of inhibitors specifically directed to upstream and downstream components of the pathway.




Biochemical and biophysical analysis of the Wnt receptor LRP6


Book Description

Der Wnt Signalweg stellt ein zentrales Regulationselement während der Embryonalentwicklung und in adulten Homöostaseprozessen dar, dessen Fehlregulierung eine wichtige Rolle in verschiedensten Krankheitsstadien spielt. LRP6 ist ein singelpass Transmembran-rezeptor, der zur Familie der Lipoproteinrezeptoren gehört und der innerhalb des Wnt/β-Catenin Signalweges als Korezeptor agiert. Die Bindung sekretierter Wnt Liganden an die extrazellulären Domänen von Frizzled und LRP6 an Empfängerzellen führt zur Aggregation von Rezeptor-Liganden Komplexen in Signalosome. Dies wird begleitet durch Serin/Threonin Phosphorylierung an Konservierten PPPSP und CK1 Motiven der intrazellulären Domäne (ICD) von LRP6, wodurch der intrazelluläre Signalweg aktiviert wird.




The Liver


Book Description

Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.