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
Metformin suppresses the expression of Sonic hedgehog in gastric cancer cells.
TL;DR: The results revealed that the protein and mRNA levels of Shh and Gli‑1 were decreased by metformin treatment in the two cell lines in a dose‑ and time‑dependent manner and the inhibitory effect of met formin on the Shh pathway was AMPK-dependent.
Journal ArticleDOI
Expression of hedgehog signalling pathway in anaplastic thyroid cancer
Ulrike Hinterseher,Annette Wunderlich,Silvia Roth,Annette Ramaswamy,Detlef K. Bartsch,Stefan Hauptmann,Brandon Greene,Volker Fendrich,S. Hoffmann +8 more
TL;DR: It is believed that the hedgehog pathway is expressed in anaplastic thyroid carcinoma specimens and proliferation of ATC cell lines can be influenced by the Hh inhibitor Cyclopamine.
Journal ArticleDOI
MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2.
Yong An,Baobao Cai,Jianmin Chen,Nan Lv,Jie Yao,Xiaofeng Xue,Min Tu,Dong Tang,Jishu Wei,Kuirong Jiang,Junli Wu,Qiang Li,Wentao Gao,Yi Miao +13 more
TL;DR: It is suggested that targeting MAP3K10 is a potential strategy for the development of alternative therapies for pancreatic cancers because of its novel and important role in the proliferation and chemoresistance of PDAC.
Journal ArticleDOI
Expression of Sonic hedgehog signaling pathway correlates with the tumorigenesis of intraductal papillary mucinous neoplasm of the pancreas.
Kennichi Satoh,Atsushi Kanno,Shin Hamada,Morihisa Hirota,Jun Umino,Atsushi Masamune,Shinichi Egawa,Fuyuhiko Motoi,Michiaki Unno,Tooru Shimosegawa +9 more
TL;DR: Findings suggested that HH signaling was activated in IPMNs and contributed to tumorigenesis in these types of neoplasms.
Journal ArticleDOI
Novel targets in esophageal and gastric cancer: beyond antiangiogenesis
TL;DR: This review will focus on novel therapeutic targets other than angiogenesis and provide a rationale for the further clinical evaluation of these agents in patients with upper gastrointestinal tract cancers.
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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Identification of the haematopoietic stem cell niche and control of the niche size
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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Journal ArticleDOI
Purification and Characterization of Mouse Hematopoietic Stem Cells
TL;DR: Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers and thirty of these cells are sufficient to save 50 percent of lethally irradiated mice, and to reconstitute all blood cell types in the survivors.
Journal ArticleDOI
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
TL;DR: The prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloids lineages is reported.
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