Journal ArticleDOI
Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours
David M. Berman,Sunil S. Karhadkar,Anirban Maitra,Rocío Montes de Oca,Meg R. Gerstenblith,Kimberly J. Briggs,Antony R. Parker,Yutaka Shimada,James R. Eshleman,D. Neil Watkins,Philip A. Beachy +10 more
TLDR
A wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathways antagonist.Abstract:
Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.read more
Citations
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Book ChapterDOI
Toward the goal of personalized therapy in pancreatic cancer by targeting the molecular phenotype.
TL;DR: A critical review of the molecular alterations in pancreatic cancer that are clinically investigated as therapeutic targets and their potential impact on clinical outcomes is provided.
Journal ArticleDOI
Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells
TL;DR: Both the invasive capacity and motility of R MS cells are significantly suppressed by Hh signaling inhibitors, demonstrating that the Hh pathway plays an important role in the invasion of RMS.
Journal ArticleDOI
Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach.
Alexander E. Sherman,Yana Zavros +1 more
TL;DR: There is a clear link between elevated Shh and signaling to gastric cancers, specifically in response to H. pylori infection.
Journal ArticleDOI
Translational advances and novel therapies for pancreatic ductal adenocarcinoma: hope or hype?
TL;DR: Current knowledge and areas where the field is advancing, and the opinion on the research direction the field should be focusing on to better deliver promising therapies for patients are given.
Journal ArticleDOI
Targeting Sonic Hedgehog: a new way to mow down pancreatic cancer?
TL;DR: This discovery is exciting and suggests that targeting Shh signaling may be an effective novel approach to therapy in patients with this devastating disease.
References
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Osteoblastic cells regulate the haematopoietic stem cell niche
Laura M. Calvi,Gregor B. Adams,Kathryn W. Weibrecht,Jonathan M. Weber,David P. Olson,M. C. Knight,Roderick P. Martin,Ernestina Schipani,P. Divieti,F. R. Bringhurst,Laurie A. Milner,Henry M. Kronenberg,David T. Scadden +12 more
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Jiwang Zhang,Chao Niu,Ling Ye,Haiyang Huang,Xi C. He,Wei Gang Tong,Jason Ross,Jeffrey S. Haug,Teri Johnson,Jian Q. Feng,Stephen E. Harris,Leanne M. Wiedemann,Leanne M. Wiedemann,Yuji Mishina,Linheng Li,Linheng Li +15 more
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Hedgehog signaling in animal development: paradigms and principles.
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Purification and Characterization of Mouse Hematopoietic Stem Cells
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Journal ArticleDOI
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
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