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

Author

Listed:
  • Anne Schuster

    (Luxembourg Institute of Health)

  • Eliane Klein

    (Luxembourg Institute of Health)

  • Virginie Neirinckx

    (Luxembourg Institute of Health)

  • Arnon Møldrup Knudsen

    (Odense University Hospital
    University of Southern Denmark)

  • Carina Fabian

    (Luxembourg Institute of Health
    University of Bergen)

  • Ann-Christin Hau

    (Luxembourg Institute of Health)

  • Monika Dieterle

    (Luxembourg Institute of Health)

  • Anais Oudin

    (Luxembourg Institute of Health)

  • Petr V. Nazarov

    (Luxembourg Institute of Health)

  • Anna Golebiewska

    (Luxembourg Institute of Health)

  • Arnaud Muller

    (Luxembourg Institute of Health)

  • Daniel Perez-Hernandez

    (Luxembourg Institute of Health)

  • Sophie Rodius

    (Luxembourg Institute of Health)

  • Gunnar Dittmar

    (Luxembourg Institute of Health)

  • Rolf Bjerkvig

    (Luxembourg Institute of Health
    University of Bergen)

  • Christel Herold-Mende

    (University of Heidelberg)

  • Barbara Klink

    (Laboratoire National de Santé
    Luxembourg Institute of Health)

  • Bjarne Winther Kristensen

    (Odense University Hospital
    University of Southern Denmark)

  • Simone P. Niclou

    (Luxembourg Institute of Health
    University of Bergen)

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.

Suggested Citation

  • Anne Schuster & Eliane Klein & Virginie Neirinckx & Arnon Møldrup Knudsen & Carina Fabian & Ann-Christin Hau & Monika Dieterle & Anais Oudin & Petr V. Nazarov & Anna Golebiewska & Arnaud Muller & Dani, 2020. "AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20029-y
    DOI: 10.1038/s41467-020-20029-y
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    Cited by:

    1. Weiwei Lin & Rui Niu & Seong-Min Park & Yan Zou & Sung Soo Kim & Xue Xia & Songge Xing & Qingshan Yang & Xinhong Sun & Zheng Yuan & Shuchang Zhou & Dongya Zhang & Hyung Joon Kwon & Saewhan Park & Chan, 2023. "IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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