Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells
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Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells. / Li, Li; Grausam, Katie B; Wang, Jun; Lun, Melody P; Ohli, Jasmin; Lidov, Hart G W; Calicchio, Monica L; Zeng, Erliang; Salisbury, Jeffrey L; Wechsler-Reya, Robert J; Lehtinen, Maria K; Schüller, Ulrich; Zhao, Haotian.
In: NAT CELL BIOL, Vol. 18, No. 4, 04.2016, p. 418-30.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells
AU - Li, Li
AU - Grausam, Katie B
AU - Wang, Jun
AU - Lun, Melody P
AU - Ohli, Jasmin
AU - Lidov, Hart G W
AU - Calicchio, Monica L
AU - Zeng, Erliang
AU - Salisbury, Jeffrey L
AU - Wechsler-Reya, Robert J
AU - Lehtinen, Maria K
AU - Schüller, Ulrich
AU - Zhao, Haotian
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
KW - Animals
KW - Blotting, Western
KW - Cell Proliferation
KW - Choroid Plexus
KW - Choroid Plexus Neoplasms
KW - Cilia
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Neoplastic
KW - Hedgehog Proteins
KW - Humans
KW - Male
KW - Mice, 129 Strain
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Microscopy, Confocal
KW - Microscopy, Electron, Transmission
KW - Oligonucleotide Array Sequence Analysis
KW - Receptor, Notch1
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Signal Transduction
KW - Tumor Cells, Cultured
KW - Tumor Microenvironment
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/ncb3327
DO - 10.1038/ncb3327
M3 - SCORING: Journal article
C2 - 26999738
VL - 18
SP - 418
EP - 430
JO - NAT CELL BIOL
JF - NAT CELL BIOL
SN - 1465-7392
IS - 4
ER -