NF1 is a tumor suppressor in neuroblastoma that determines retinoic acid response and disease outcome.

Cell
Michael HölzelRené Bernards

Abstract

Retinoic acid (RA) induces differentiation of neuroblastoma cells in vitro and is used with variable success to treat aggressive forms of this disease. This variability in clinical response to RA is enigmatic, as no mutations in components of the RA signaling cascade have been found. Using a large-scale RNAi genetic screen, we identify crosstalk between the tumor suppressor NF1 and retinoic acid-induced differentiation in neuroblastoma. Loss of NF1 activates RAS-MEK signaling, which in turn represses ZNF423, a critical transcriptional coactivator of the retinoic acid receptors. Neuroblastomas with low levels of both NF1 and ZNF423 have extremely poor outcome. We find NF1 mutations in neuroblastoma cell lines and in primary tumors. Inhibition of MEK signaling downstream of NF1 restores responsiveness to RA, suggesting a therapeutic strategy to overcome RA resistance in NF1-deficient neuroblastomas.

References

Oct 31, 1985·The New England Journal of Medicine·R C SeegerD Hammond
Nov 1, 1995·Archives of Pediatrics & Adolescent Medicine·J L Cotton, R G Williams
Jan 1, 1993·Nature Genetics·I TheA Bernards
Jan 25, 1996·The New England Journal of Medicine·H CaronR Versteeg
Jun 1, 1997·Cancer Genetics and Cytogenetics·T MartinssonP Kogner
Jan 15, 2002·Nature Neuroscience·Jiayuan TongYi Zhong
Apr 11, 2003·American Journal of Medical Genetics. Part a·Paola OrigoneGian Paolo Tonini
Aug 13, 2003·The European Journal of Neuroscience·P J McCafferyE Rosa-Molinar
Nov 2, 2004·Oncogene·Vera van LimptRogier Versteeg
Nov 25, 2005·The New England Journal of Medicine·Edward F AttiyehUNKNOWN Children's Oncology Group
Feb 14, 2006·Nature Chemical Biology·Thijn R BrummelkampRoderick L Beijersbergen
Sep 1, 2006·Familial Cancer·Siân GriffithsMeena Upadhyaya
Sep 7, 2006·Journal of the National Cancer Institute·Shahab AsgharzadehRobert C Seeger
Nov 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·André OberthuerMatthias Fischer
Oct 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mirjam T EppingRené Bernards
Feb 13, 2008·Molecular and Cellular Biology·Margaret P QuinlanJeffrey Settleman
Oct 24, 2008·The New England Journal of Medicine·Christos S KarapetisJohn R Zalcberg
Jul 4, 2009·Cancer Cell·Lauren T McGillicuddyKaren Cichowski
Sep 10, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yael P MosséJohn M Maris

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Citations

Mar 10, 2011·Nature Medicine·Ian J Majewski, René Bernards
Sep 26, 2013·Nature Reviews. Cancer·Bengt Hallberg, Ruth H Palmer
Jul 28, 2011·Briefings in Functional Genomics·Eric Campeau, Stéphane Gobeil
Sep 11, 2012·Human Molecular Genetics·Nelly BurnichonAnne-Paule Gimenez-Roqueplo
Jul 18, 2012·Genes & Development·Andrea I McClatchey, Karen Cichowski
Jun 19, 2013·Molecular and Cellular Biology·Prashanth Kumar BajpeSidong Huang
Mar 20, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kristina A Cole, John M Maris
Nov 23, 2012·Cancer Discovery·Ophélia MaertensKaren Cichowski
May 31, 2011·Journal of Translational Medicine·Thomas G P GrunewaldStefan Burdach
Dec 14, 2011·Human Genomics·Sebastian Laycock-van SpykMeena Upadhyaya
Jun 13, 2013·Endocrine-related Cancer·Jenny WelanderOliver Gimm
Feb 11, 2014·Journal of the National Cancer Institute·Klaus G GriewankRajmohan Murali
May 13, 2014·Advances in Biological Regulation·Ophélia Maertens, Karen Cichowski
Feb 11, 2014·Oncogene·M E BrundageN Ratner
Oct 1, 2011·Expert Review of Neurotherapeutics·William Clay Gustafson, Katherine K Matthay
Mar 14, 2013·Expert Opinion on Medical Diagnostics·Samuel NavarroRosa Noguera
May 3, 2016·The Journal of Nutritional Biochemistry·Jen-Kit TanWan Zurinah Wan Ngah
Feb 9, 2016·Progress in Neurobiology·Annette C BakkerMarco Nievo
Dec 23, 2015·Trends in Genetics : TIG·Xueda Hu, Zemin Zhang
Nov 13, 2012·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Katrien Berns, René Bernards
Jul 7, 2012·Biochemical and Biophysical Research Communications·Jingbo QiaoDai H Chung
Feb 7, 2012·Trends in Biotechnology·Qiuwei PanMaikel P Peppelenbosch
Jan 28, 2012·Biochemical Pharmacology·Jessica CharletMarc Diederich
Jan 6, 2016·Molecular Cancer·Constanza L CortesAlbert Tauler
Jun 15, 2011·American Journal of Medical Genetics. Part a·Franck BourdeautOlivier Delattre
Sep 6, 2012·International Journal of Cancer. Journal International Du Cancer·Patrick A MayesJohn M Maris
Sep 14, 2010·Journal of Cellular Physiology·Lorraine J Gudas, John A Wagner
Sep 14, 2013·Cancer Cell·Sara Koenig McLaughlinKaren Cichowski
May 24, 2013·Pediatric Hematology and Oncology·Hong MeiQiangsong Tong

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