Dexamethasone destabilizes Nmyc to inhibit the growth of hedgehog-associated medulloblastoma.
Dexamethasone destabilizes Nmyc to inhibit the growth of hedgehog-associated medulloblastoma.
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DOI：
10.1158/0008-5472.can-10-0554
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发表时间：
2010-07-01
期刊：
影响因子：
11.2
通讯作者：
Schüller U
中科院分区：
文献类型：
--
作者：
Heine VM;Priller M;Ling J;Rowitch DH;Schüller U
Mouse studies indicate that the synthetic glucocorticoid Dexamethasone (Dex) impairs the proliferation of granule neuron precursors in the cerebellum, which are transformed to medulloblastoma by activation of Sonic hedgehog (Shh) signaling. Here we show that Dex treatment also inhibits Shh-induced tumor growth, enhancing survival of tumor-prone transgenic mice. We found that Nmyc was specifically required in granule cells for Shh-induced tumorigenesis and that Dex acted to reduce Nmyc protein levels. Moreover, we found that Dex-induced destabilization of Nmyc is mediated by activation of GSK3β, which targets Nmyc for proteasomal degradation. Together, our findings show that Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma.
