Arsenic trioxide inhibits tumor cell growth in malignant rhabdoid tumors in vitro and in vivo by targeting overexpressed Gli1

Kornelius Kerl, Natalia Moreno, Till Holsten, Julia Ahlfeld, Julius Mertins, Marc Hotfilder, Marcel Kool, Kerstin Bartelheim, Sabine Schleicher, Rupert Handgretinger, Ulrich Schüller, Michael Meisterernst, Michael C. Frühwald

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41 Citations (Scopus)

Abstract

Rhabdoid tumors are highly aggressive tumors occurring in infants and very young children. Despite multimodal and intensive therapy prognosis remains poor. Molecular analyses have uncovered several deregulated pathways, among them the CDK4/6-Rb-, the WNT- and the Sonic hedgehog (SHH) pathways. The SHH pathway is activated in rhabdoid tumors by GLI1 overexpression. Here, we demonstrate that arsenic trioxide (ATO) inhibits tumor cell growth of malignant rhabdoid tumors in vitro and in a mouse xenograft model by suppressing Gli1. Our data uncover ATO as a promising therapeutic approach to improve prognosis for rhabdoid tumor patients.

Original languageEnglish
Pages (from-to)989-995
Number of pages7
JournalInternational Journal of Cancer
Volume135
Issue number4
DOIs
Publication statusPublished - 15 Aug 2014
Externally publishedYes

Keywords

  • arsenic trioxide
  • Gli1
  • rhabdoid tumors
  • Sonic hedgehog

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