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@ARTICLE{He:120198,
author = {X. He and L. Zhang and Y. Chen and M. Remke and D. Shih and
F. Lu and H. Wang and Y. Deng and Y. Yu and Y. Xia and X. Wu
and V. Ramaswamy and T. Hu and F. Wang and W. Zhou and D. K.
Burns and S. H. Kim and M. Kool$^*$ and S. Pfister$^*$ and
L. S. Weinstein and S. L. Pomeroy and R. J. Gilbertson and
J. B. Rubin and Y. Hou and R. Wechsler-Reya and M. D. Taylor
and Q. R. Lu},
title = {{T}he {G} protein α subunit {G}αs is a tumor suppressor
in {S}onic hedgehog-driven medulloblastoma.},
journal = {Nature medicine},
volume = {20},
number = {9},
issn = {1546-170X},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DKFZ-2017-00780},
pages = {1035 - 1042},
year = {2014},
abstract = {Medulloblastoma, the most common malignant childhood brain
tumor, exhibits distinct molecular subtypes and cellular
origins. Genetic alterations driving medulloblastoma
initiation and progression remain poorly understood. Herein,
we identify GNAS, encoding the G protein Gαs, as a potent
tumor suppressor gene that, when expressed at low levels,
defines a subset of aggressive Sonic hedgehog (SHH)-driven
human medulloblastomas. Ablation of the single Gnas gene in
anatomically distinct progenitors in mice is sufficient to
induce Shh-associated medulloblastomas, which recapitulate
their human counterparts. Gαs is highly enriched at the
primary cilium of granule neuron precursors and suppresses
Shh signaling by regulating both the cAMP-dependent pathway
and ciliary trafficking of Hedgehog pathway components.
Elevation in levels of a Gαs effector, cAMP, effectively
inhibits tumor cell proliferation and progression in
Gnas-ablated mice. Thus, our gain- and loss-of-function
studies identify a previously unrecognized tumor suppressor
function for Gαs that can be found consistently across
Shh-group medulloblastomas of disparate cellular and
anatomical origins, highlighting G protein modulation as a
potential therapeutic avenue.},
keywords = {Hedgehog Proteins (NLM Chemicals) / Cyclic AMP (NLM
Chemicals) / GTP-Binding Protein alpha Subunits, Gs (NLM
Chemicals)},
cin = {B062},
ddc = {610},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25150496},
pmc = {pmc:PMC4334261},
doi = {10.1038/nm.3666},
url = {https://inrepo02.dkfz.de/record/120198},
}