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
More filters
Journal ArticleDOI
Shh signaling and pancreatic cancer: implications for therapy?
TL;DR: Results showing that activated hedgehog signaling enhances the proliferation and survival of pancreatic duct epithelial cells, the presumptive target cells for PDAC development, and that sonic hedgehog (Shh) expression was sufficient to initiate the formation of early pancreatic lesions are discussed.
Journal Article
The Hedgehog Pathway Is a Possible Therapeutic Target for Patients with Estrogen Receptor-negative Breast Cancer
Chizu Kameda,Haruo Tanaka,Akio Yamasaki,Masafumi Nakamura,Kenichiro Koga,Norihiro Sato,Makoto Kubo,Syoji Kuroki,Masao Tanaka,Mitsuo Katano +9 more
TL;DR: Since the previous data have shown a constitutive activation of the Hh pathway in surgically-resected ERalpha-negative breast cancer specimens, the HH pathway, especially Gli1, may be a useful therapeutic target for patients with ER alpha- negative breast cancer.
Journal ArticleDOI
Hedgehog/GLI-mediated transcriptional inhibitors from Zizyphus cambodiana.
Midori A. Arai,Chikashi Tateno,Takahiro Hosoya,Takashi Koyano,Thaworn Kowithayakorn,Masami Ishibashi +5 more
TL;DR: These pentacyclic triterpene inhibitors showed an important relationship between Hh/GLI signaling inhibition, the decrease of BCL2, and cytotoxicity against cancer cells.
Journal ArticleDOI
Hedgehog pathway signaling in cervical carcinoma and outcome after chemoradiation
Naz Chaudary,Melania Pintilie,David W. Hedley,David W. Hedley,David W. Hedley,Anthony Fyles,Anthony Fyles,Michael Milosevic,Michael Milosevic,Blaise A. Clarke,Richard P. Hill,Richard P. Hill,Helen Mackay +12 more
TL;DR: In this article, the authors examined associations between Hh gene expression and measurements of HP5 (the percentage of oxygen pressure readings in each tumor <5 mm Hg) and interstitial fluid pressure (IFP) and concluded that further investigation into this pathway after radiation and Hh inhibition are warranted.
Journal ArticleDOI
Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells
TL;DR: In response to injury, Hedgehog signaling regulates the production of Upd2 in enteroblasts, which in turn activates the JAK–STAT pathway to drive intestinal stem cell proliferation.
References
More filters
Journal ArticleDOI
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
TL;DR: Osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation.
Journal ArticleDOI
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
TL;DR: It is concluded that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of H SCs by regulating niche size.
Journal ArticleDOI
Hedgehog signaling in animal development: paradigms and principles.
TL;DR: In their screen for mutations that disrupt the Drosophila larval body plan, these authors identified several that cause the duplication of denticles and an accompanying loss of naked cuticle, characteristic of the posterior half of each segment.
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.
Related Papers (5)
Hedgehog signaling in animal development: paradigms and principles.
Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome
Heidi Hahn,Carol Wicking,Peter G. Zaphiropoulos,Mae R. Gailani,Susan Shanley,Abirami Chidambaram,Igor Vorechovsky,Erika Holmberg,Anne Birgitte Undén,Susan Gillies,Kylie Negus,Ian M. Smyth,Carolyn Pressman,David J. Leffell,Bernard Gerrard,Alisa M. Goldstein,Michael Dean,Rune Toftgård,Georgia Chenevix-Trench,Brandon J. Wainwright,Allen E. Bale +20 more