Dexamethasone destabilizes Nmyc to inhibit the growth of hedgehog-associated medulloblastoma

Vivi M Heine, Markus Priller, Jason Ling, David H Rowitch, Ulrich Schüller

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)


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 the 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 glycogen synthase kinase 3beta, which targets Nmyc for proteasomal degradation. Together, our findings show that Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma.

Original languageEnglish
Pages (from-to)5220-5
Number of pages6
JournalCancer research
Issue number13
Publication statusPublished - 1 Jul 2010


  • Animals
  • Brain Neoplasms/drug therapy
  • Dexamethasone/pharmacology
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3/metabolism
  • Hedgehog Proteins/antagonists & inhibitors
  • Medulloblastoma/drug therapy
  • Mice
  • Mice, Transgenic
  • Phosphorylation
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-myc/antagonists & inhibitors
  • Signal Transduction
  • Tumor Cells, Cultured

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