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001     119945
005     20240228135002.0
024 7 _ |a 10.1016/j.devcel.2014.08.010
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024 7 _ |a pmid:25263791
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024 7 _ |a 1534-5807
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024 7 _ |a 1878-1551
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037 _ _ |a DKFZ-2017-00536
041 _ _ |a eng
082 _ _ |a 570
100 1 _ |a Mille, Frédéric
|b 0
245 _ _ |a The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors.
260 _ _ |a Cambridge, Mass.
|c 2014
|b Cell Press
336 7 _ |a article
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336 7 _ |a Journal Article
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520 _ _ |a During cerebellar development, Sonic hedgehog (Shh) signaling drives the proliferation of granule cell precursors (GCPs). Aberrant activation of Shh signaling causes overproliferation of GCPs, leading to medulloblastoma. Although the Shh-binding protein Boc associates with the Shh receptor Ptch1 to mediate Shh signaling, whether Boc plays a role in medulloblastoma is unknown. Here, we show that BOC is upregulated in medulloblastomas and induces GCP proliferation. Conversely, Boc inactivation reduces proliferation and progression of early medulloblastomas to advanced tumors. Mechanistically, we find that Boc, through elevated Shh signaling, promotes high levels of DNA damage, an effect mediated by CyclinD1. High DNA damage in the presence of Boc increases the incidence of Ptch1 loss of heterozygosity, an important event in the progression from early to advanced medulloblastoma. Together, our results indicate that DNA damage promoted by Boc leads to the demise of its own coreceptor, Ptch1, and consequently medulloblastoma progression.
536 _ _ |a 312 - Functional and structural genomics (POF3-312)
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588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Boc protein, mouse
|2 NLM Chemicals
650 _ 7 |a Hedgehog Proteins
|2 NLM Chemicals
650 _ 7 |a Immunoglobulin G
|2 NLM Chemicals
650 _ 7 |a PTCH protein, human
|2 NLM Chemicals
650 _ 7 |a Patched Receptors
|2 NLM Chemicals
650 _ 7 |a Patched-1 Receptor
|2 NLM Chemicals
650 _ 7 |a Ptch1 protein, mouse
|2 NLM Chemicals
650 _ 7 |a Receptors, Cell Surface
|2 NLM Chemicals
650 _ 7 |a Shh protein, mouse
|2 NLM Chemicals
650 _ 7 |a Cyclin D1
|0 136601-57-5
|2 NLM Chemicals
700 1 _ |a Tamayo-Orrego, Lukas
|b 1
700 1 _ |a Lévesque, Martin
|b 2
700 1 _ |a Remke, Marc
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700 1 _ |a Korshunov, Andrey
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700 1 _ |a Cardin, Julie
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700 1 _ |a Bouchard, Nicolas
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700 1 _ |a Izzi, Luisa
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700 1 _ |a Kool, Marcel
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700 1 _ |a Northcott, Paul A
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700 1 _ |a Taylor, Michael D
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700 1 _ |a Pfister, Stefan
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700 1 _ |a Charron, Frédéric
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773 _ _ |a 10.1016/j.devcel.2014.08.010
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