Journal Article

DKFZ-2017-00780

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog-driven medulloblastoma.

He, X. ; Zhang, L. ; Chen, Y. ; Remke, M. ; Shih, D. ; Lu, F. ; Wang, H. ; Deng, Y. ; Yu, Y. ; Xia, Y. ; Wu, X. ; Ramaswamy, V. ; Hu, T. ; Wang, F. ; Zhou, W. ; Burns, D. K. ; Kim, S. H. ; Kool, M.DKFZ* ; Pfister, S.DKFZ* ; Weinstein, L. S. ; Pomeroy, S. L. ; Gilbertson, R. J. ; Rubin, J. B. ; Hou, Y. ; Wechsler-Reya, R. ; Taylor, M. D. ; Lu, Q. R.

2014
Nature America Inc. New York, NY

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/nm.3666

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.

Keyword(s): Hedgehog Proteins ; Cyclic AMP ; GTP-Binding Protein alpha Subunits, Gs

---

Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2014

---

Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---