TY - JOUR
T1 - AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion
AU - Schuster, Anne
AU - Klein, Eliane
AU - Neirinckx, Virginie
AU - Knudsen, Arnon Møldrup
AU - Fabian, Carina
AU - Hau, Ann Christin
AU - Dieterle, Monika
AU - Oudin, Anais
AU - Nazarov, Petr V.
AU - Golebiewska, Anna
AU - Muller, Arnaud
AU - Perez-Hernandez, Daniel
AU - Rodius, Sophie
AU - Dittmar, Gunnar
AU - Bjerkvig, Rolf
AU - Herold-Mende, Christel
AU - Klink, Barbara
AU - Kristensen, Bjarne Winther
AU - Niclou, Simone P.
N1 - Funding Information:
We thank Virginie Baus and Vanessa Barthelemy for technical assistance and are grateful for the financial support of the Fondation Cancer Luxembourg (INVGBM and Pan-RTK Targeting), Télévie-FNRS (GBModImm no 7.8513.18 and TETHER no 7.4615.18) and the Luxembourg National Research Fund (FNR; CORE Junior C17/BM/11664971/ DEMICS).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097438590&partnerID=8YFLogxK
UR - https://www.ncbi.nlm.nih.gov/pubmed/33311477
U2 - 10.1038/s41467-020-20029-y
DO - 10.1038/s41467-020-20029-y
M3 - Article
C2 - 33311477
AN - SCOPUS:85097438590
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6366
ER -