AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion.

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Anne Schuster - (Autor:in)
  • Eliane Klein - (Autor:in)
  • Virginie Neirinckx - (Autor:in)
  • Arnon Moldrup Knudsen - (Autor:in)
  • Carina Fabian - , Luxembourg Institute of Health, University of Bergen (Autor:in)
  • Ann-Christin Hau - (Autor:in)
  • Monika Dieterle - (Autor:in)
  • Anais Oudin - (Autor:in)
  • Petr V. Nazarov - (Autor:in)
  • Anna Golebiewska - (Autor:in)
  • Arnaud Muller - (Autor:in)
  • Daniel Perez-Hernandez - (Autor:in)
  • Sophie Rodius - (Autor:in)
  • Gunnar Dittmar - (Autor:in)
  • Rolf Bjerkvig - (Autor:in)
  • Christel Herold-Mende - (Autor:in)
  • Barbara Klink - , Institut für Klinische Genetik (Autor:in)
  • Bjarne Winther Kristensen - (Autor:in)
  • Simone P. Niclou - (Autor:in)

Abstract

The infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the efficacy of systemic treatment. Here, we use a genome-wide interference screen to determine invasion-essential genes and identify the AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of GBM invasion. Using patient-derived cellular models, we show that loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive. At the mechanistic level, we find that ZFAND3 activity requires nuclear localization and integral zinc-finger domains. Our findings indicate that ZFAND3 acts within a nuclear protein complex to activate gene transcription and regulates the promoter of invasion-related genes such as COL6A2, FN1, and NRCAM. Further investigation in ZFAND3 function in GBM and other invasive cancers is warranted.

Details

OriginalspracheEnglisch
Aufsatznummer6366
FachzeitschriftNature communications
Jahrgang11
PublikationsstatusVeröffentlicht - 11 Dez. 2020
Peer-Review-StatusJa

Externe IDs

PubMed 33311477
PubMed PMC7732990
Scopus 85097438590

Schlagworte