Journal article
Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells
Nature cell biology, Vol.18(4), pp.418-430
04/2016
DOI: 10.1038/ncb3327
PMCID: PMC4814324
PMID: 26999738
Abstract
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.
Details
- Title: Subtitle
- Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells
- Creators
- Li Li - Children's Health Research Center, Sanford Research, 2301 E 60th Street North, Sioux Falls, South Dakota 57104, USAKatie B Grausam - Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 E. Clark Street, Vermillion, South Dakota 57069, USAJun Wang - Tumor Initiation and Maintenance Programme, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USAMelody P Lun - Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USAJasmin Ohli - Center for Neuropathology and Prion Research, Ludwig-Maximilans-University, 81377 Munich, GermanyHart G W Lidov - Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USAMonica L Calicchio - Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USAErliang Zeng - Department of Computer Science, University of South Dakota, 414 E. Clark Street, Vermillion, South Dakota 57069, USAJeffrey L Salisbury - Microscopy and Cell Analysis Core, Mayo Clinic (Guggenheim-14), 200 First Street SW., Rochester, Minnesota 55905, USARobert J Wechsler-Reya - Tumor Initiation and Maintenance Programme, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USAMaria K Lehtinen - Department of Pathology, Boston Children's Hospital, Boston, Massachusetts 02115, USAUlrich Schüller - Center for Neuropathology and Prion Research, Ludwig-Maximilans-University, 81377 Munich, GermanyHaotian Zhao - Department of Chemistry and Biochemistry, South Dakota State University, Avera Health Science Center (SAV) 131, Brookings, South Dakota 57007, USA
- Resource Type
- Journal article
- Publication Details
- Nature cell biology, Vol.18(4), pp.418-430
- DOI
- 10.1038/ncb3327
- PMID
- 26999738
- PMCID
- PMC4814324
- NLM abbreviation
- Nat Cell Biol
- ISSN
- 1465-7392
- eISSN
- 1476-4679
- Publisher
- England
- Grant note
- P30 HD018655 / NICHD NIH HHS P20 GM103548 / NIGMS NIH HHS P30 HD18655 / NICHD NIH HHS P20 GM103620 / NIGMS NIH HHS 1P20GM10362001A1 / NIGMS NIH HHS 1S10OD016167 / NIH HHS 5P20GM103548 / NIGMS NIH HHS S10 OD016167 / NIH HHS
- Language
- English
- Date published
- 04/2016
- Academic Unit
- Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Biostatistics; Dental Research
- Record Identifier
- 9984070681002771
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