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
Induction of MITF expression in human cholangiocarcinoma cells and hepatocellular carcinoma cells by cyclopamine, an inhibitor of the Hedgehog signaling.
Papavee Samatiwat,Kazuhisa Takeda,Soisungwan Satarug,Koji Ohba,Veerapol Kukongviriyapan,Shigeki Shibahara +5 more
TL;DR: It is shown that MITF-A mRNA is predominantly expressed in all three human liver cancer cell lines examined, and cyclopamine, an inhibitor of the Hedgehog signalling, increased the expression levels of MITF proteins in HuCCT1 and HepG2 cells, but not in KKU-100 cells, suggesting thatMITF expression may be down-regulated in some liver cancer cases.
Journal ArticleDOI
Genetic landscape and ligand-dependent activation of sonic hedgehog-Gli1 signaling in chordomas: a novel therapeutic target
Chenlong Yang,Lei Yong,Chen Liang,Yan Li,Yunlong Ma,Feng Wei,Liang Jiang,Hua Zhou,Guanping He,Xiaoyu Pan,Bao Hai,Jian Wu,Yulun Xu,Zhongjun Liu,Xiaoguang Liu +14 more
TL;DR: Vismodegib significantly inhibited cell proliferation and induced apoptosis and G1/S cell cycle arrest and may be a promising targeted agent for chordoma treatment, and further clinical trials are warranted.
Journal ArticleDOI
WISP-1 induced by mechanical stress contributes to fibrosis and hypertrophy of the ligamentum flavum through Hedgehog-Gli1 signaling.
TL;DR: In this article, the authors found that Gli1 was upregulated in hypertrophic ligamentum flavum (LF) tissues and required for fibrogenesis in fibroblasts.
Journal ArticleDOI
Molecular biology, models, and histopathology of chronic pancreatitis and pancreatic cancer
TL;DR: The treatment for both conditions has improved over the past decades, overall prognosis remains poor necessitating the development of new treatment options, which in turn requires a deeper understanding of the underlying pathophysiology including genetic, molecular, and histopathologic changes occurring in both diseases.
Journal ArticleDOI
Hedgehog signaling pathway mediates tongue tumorigenesis in wild-type mice but not in Gal3-deficient mice.
Débora de Oliveira Santos,Adriano Mota Loyola,Sérgio Vitorino Cardoso,Roger Chammas,Fu-Tong Liu,Paulo Rogério de Faria +5 more
TL;DR: The results suggest that activated Wnt signaling is present in both mice, and that the Hh signaling pathway might play a role in tongue carcinoma development in Gal3+/+ mice.
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.
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.
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