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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Journal ArticleDOI
Sonic hedgehog signaling in basal cell carcinomas
TL;DR: The molecular mechanisms involved in alterations of the hedgehog signaling pathway that lead to the formation of basal cell carcinomas are being unraveled and has already allowed the investigation of future therapeutic strategies for treating these skin cancers.
Journal ArticleDOI
Suppressing Wnt Signaling by the Hedgehog Pathway through sFRP-1
Jing He,Tao Sheng,Arwen A. Stelter,Chengxin Li,Xiaoli Zhang,Mala Sinha,Bruce A. Luxon,Jingwu Xie +7 more
TL;DR: It is reported that expression of a secreted frizzled-related protein-sFRP-1 in mouse embryonic fibroblasts is dependent on Gli1 and Gli2, and data indicate that sFRp-1, a target gene of the hedgehog pathway, is involved in cross-talk between the Hedgehog pathway and the Wnt pathway.
Journal ArticleDOI
Hedgehog signaling pathway and gastric cancer.
Yuriko Katoh,Masaru Katoh +1 more
TL;DR: Hedgehog, WNT, FGF and BMP signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis, which leads to aberrant activation of Hedgehog signaling through PTCH1 to GLI1 in gastric cancer.
Journal ArticleDOI
Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells.
Moneeb Ehtesham,Anuraag Sarangi,Juan G. Valadez,S Chanthaphaychith,M W Becher,Ty W. Abel,Reid C. Thompson,Michael K. Cooper +7 more
TL;DR: Findings suggest a regulatory role for the Hh pathway in progenitor cells within grade II and III gliomas, and the potential clinical utility of monitoring and targeting this pathway in these primary brain tumors.
Journal ArticleDOI
Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas.
TL;DR: These results provide a unique view of the tumor-initiating effects of oncogenic KRAS in a living vertebrate organism, and suggest that zebrafish models of pancreatic cancer may prove useful in advancing the understanding of the human 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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A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
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