title: Arsenic trioxide inhibits tumor cell growth in malignant rhabdoid tumors in vitro and in vivo by targeting overexpressed Gli1.
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.
authors.affiliation: Institute of Molecular Tumor Biology, Westfalian Wilhelms University, Muenster, Germany; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.
authors.forename: Kornelius
authors.initials: K
authors.lastname: Kerl
authors.forename: Natalia
authors.initials: N
authors.lastname: Moreno
authors.forename: Till
authors.initials: T
authors.lastname: Holsten
authors.forename: Julia
authors.initials: J
authors.lastname: Ahlfeld
authors.forename: Julius
authors.initials: J
authors.lastname: Mertins
authors.forename: Marc
authors.initials: M
authors.lastname: Hotfilder
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bartelheim
authors.forename: Sabine
authors.initials: S
authors.lastname: Schleicher
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schüller
authors.forename: Michael
authors.initials: M
authors.lastname: Meisterernst
authors.forename: Michael C
authors.initials: MC
authors.lastname: Frühwald
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle; D049109:Cell Proliferation; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010087:Oxides / Q000494:pharmacology*; D011379:Prognosis; D018335:Rhabdoid Tumor / Q000188:drug therapy*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; C400551:GLI1 protein, human; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D010087:Oxides; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000077237:Arsenic Trioxide
keywords: Gli1; Sonic hedgehog; arsenic trioxide; rhabdoid tumors