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
Development of anticancer agents targeting the Hedgehog signaling.
TL;DR: The therapeutic agents for inhibition of the Hedgehog signaling and their clinical advances in cancer treatment are reviewed.
Journal ArticleDOI
Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal
TL;DR: Defect in feedback between the two morphogens explains both phenotypes, and disruption of a balance between the morphogen targets further accounts for the local overgrowth.
Journal ArticleDOI
Dual blockade of phosphatidylinositol 3′-kinase and mitogen-activated protein kinase pathways overcomes paclitaxel-resistance in colorectal cancer
Rui Xu,Kenji Nakano,Hironori Iwasaki,Michiaki Kumagai,Rie Wakabayashi,Akio Yamasaki,Hiroyuki Suzuki,Ryuichi Mibu,Hideya Onishi,Mitsuo Katano +9 more
TL;DR: PI3K is involved in low susceptibility of colorectal cancer to pac litaxel and dual PI3K/MAPK targeting agents may evolve a new paclitaxel-based chemotherapy for coloreCTal cancer.
Book ChapterDOI
Hedgehog and Vitamin D Signaling Pathways in Development and Disease.
TL;DR: Calcitriol and several structurally related members of the vitamin D class of seco-steroids have demonstrated the ability to regulate the hedgehog (Hh) signaling pathway, suggesting a cooperative role during multiple stages of human development and disease.
Journal ArticleDOI
Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract.
Hui Lin,Glenn A. Jackson,Yuan Lu,Sara K. Drenkhahn,Korey J. Brownstein,Korey J. Brownstein,Nicholas J.E. Starkey,William R. Lamberson,Kevin L. Fritsche,Valeri V. Mossine,Cynthia Besch-Williford,William R. Folk,Yong Zhang,Dennis B. Lubahn +13 more
TL;DR: Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli‐reporter activity in Shh Light II cells, which suggests that the S. frutescens extract may exert anti‐cancer effect by targeting Gli/Hh signaling, and Sutherlandiosides D is one of the active compounds.
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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Journal ArticleDOI
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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