Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells.

Autor: Li L; Children's Health Research Center, Sanford Research, 2301 E 60th Street North, Sioux Falls, South Dakota 57104, USA., Grausam KB; Children's Health Research Center, Sanford Research, 2301 E 60th Street North, Sioux Falls, South Dakota 57104, USA.; Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 E. Clark Street, Vermillion, South Dakota 57069, USA., Wang J; Tumor Initiation and Maintenance Programme, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA., Lun MP; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA., Ohli J; Center for Neuropathology and Prion Research, Ludwig-Maximilans-University, 81377 Munich, Germany., Lidov HG; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USA., Calicchio ML; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USA., Zeng E; Department of Biology, University of South Dakota, 414 E. Clark Street, Vermillion, South Dakota 57069, USA.; Department of Computer Science, University of South Dakota, 414 E. Clark Street, Vermillion, South Dakota 57069, USA., Salisbury JL; Department of Biochemistry and Molecular Biology, Mayo Clinic (Guggenheim-14), 200 First Street SW., Rochester, Minnesota 55905, USA.; Microscopy and Cell Analysis Core, Mayo Clinic (Guggenheim-14), 200 First Street SW., Rochester, Minnesota 55905, USA., Wechsler-Reya RJ; Tumor Initiation and Maintenance Programme, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA., Lehtinen MK; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USA., Schüller U; Center for Neuropathology and Prion Research, Ludwig-Maximilans-University, 81377 Munich, Germany., Zhao H; Children's Health Research Center, Sanford Research, 2301 E 60th Street North, Sioux Falls, South Dakota 57104, USA.; Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 E. Clark Street, Vermillion, South Dakota 57069, USA.; Cancer Biology Research Center, Sanford Research, 2301 E 60th Street North, Sioux Falls, South Dakota 57104, USA.; Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, 1400 W 22nd Street, Sioux Falls, South Dakota 57105, USA.; Department of Chemistry and Biochemistry, South Dakota State University, Avera Health Science Center (SAV) 131, Brookings, South Dakota 57007, USA.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2016 Apr; Vol. 18 (4), pp. 418-30. Date of Electronic Publication: 2016 Mar 21.
DOI: 10.1038/ncb3327
Abstrakt: Aberrant Notch signalling has been linked to many cancers including choroid plexus (CP) tumours, a group of rare and predominantly paediatric brain neoplasms. We developed animal models of CP tumours, by inducing sustained expression of Notch1, that recapitulate properties of human CP tumours with aberrant NOTCH signalling. Whole-transcriptome and functional analyses showed that tumour cell proliferation is associated with Sonic Hedgehog (Shh) in the tumour microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumour cells possess a solitary primary cilium as a result of Notch-mediated suppression of multiciliate differentiation. A Shh-driven signalling cascade in the primary cilium occurs in tumour cells but not in epithelial cells. Lineage studies show that CP tumours arise from monociliated progenitors in the roof plate characterized by elevated Notch signalling. Abnormal SHH signalling and distinct ciliogenesis are detected in human CP tumours, suggesting the SHH pathway and cilia differentiation as potential therapeutic avenues.
Databáze: MEDLINE
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