@article{e5a4106ff06a4573bfa595a1f99650c0,
title = "Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells",
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.",
author = "Li Li and Grausam, {Katie B.} and Jun Wang and Lun, {Melody P.} and Jasmin Ohli and Lidov, {Hart G.W.} and Calicchio, {Monica L.} and Erliang Zeng and Salisbury, {Jeffrey L.} and Wechsler-Reya, {Robert J.} and Lehtinen, {Maria K.} and Ulrich Sch{\"u}ller and Haotian Zhao",
note = "Funding Information: We thank all members of the laboratory for helpful discussions. We are grateful to K. Millen (Seattle Children's Hospital Research Institute, USA), J. Kim (University of Texas Southwestern Medical Center, USA) and R. Kageyama (Institute for Virus Research Kyoto University, Japan) for providing the Lmx1a-Cre transgenic mouse strain, Smo antibody, and Hes1 antibodies, respectively, and C. Eberhart (Johns Hopkins University School of Medicine, USA), M. Taylor (The Hospital for Sick Children, Canada) and S. Santagata (Boston Children'sHospital, USA) for providing human CP tumour samples. We wish to acknowledge the Labatt Brain Tumour Research Centre Tumour and Tissue Repository, which is supported by b.r.a.i.n child and Meagan'sWalk.We are indebted to C. Evans, A. Kelsch and E. Grandprey for excellent technical assistance. We thank W.K. Miskimins and K. Surendran for helpful suggestions, and J. Tao and D. Maher for critical reading of the manuscript and helpful discussions. This project is supported by: Boston Children's Hospital IDDRC P30 HD18655, Sanford Research, and Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under grant number 5P20GM103548 (Cancer), which also supports Cores at Sanford Research together with NIH grant 1P20GM103620- 01A1 (Pediatrics). The RNA In Situ Hybridization Core facility at Baylor College of Medicine is supported by a Shared Instrumentation grant from the NIH (1S10OD016167). Additional support was provided by the National Brain Tumor Society (R.J.W.-R.). Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited.",
year = "2016",
month = mar,
day = "30",
doi = "10.1038/ncb3327",
language = "English (US)",
volume = "18",
pages = "418--430",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "4",
}