Nuclear factor one B (NFIB) encodes a subtype-specific tumour suppressor in glioblastoma

// Brett W. Stringer 1, 2 , Jens Bunt 3 , Bryan W. Day 1, 2 , Guy Barry 3 , Paul R. Jamieson 1, 2 , Kathleen S. Ensbey 1, 2 , Zara C. Bruce 1, 2 , Kate Goasdoué 1, 2 , Hélène Vidal 1, 2 , Sara Charmsaz 2 , Fiona M. Smith 2 , Leanne T. Cooper 2 , Michael Piper 3, 4 , Andrew W. Boyd 1, 2, 5, * , Linda J. Richards 3, 4, * 1 Brain Cancer Research Unit, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia 2 Leukaemia Foundation Research Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia 3 Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Queensland, Australia 4 School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Queensland, Australia 5 Department of Medicine, The University of Queensland, Brisbane, 4072, Queensland, Australia * Co-senior authors Correspondence to: Brett W. Stringer, e-mail: Brett.Stringer@qimrberghofer.edu.au Michael Piper, e-mail: m.piper@uq.edu.au Andrew W. Boyd, e-mail: Andrew.Boyd@qimrberghofer.edu.au Linda J. Richards, e-mail: richards@uq.edu.au Keywords: glioblastoma (GBM), glioma, nuclear factor I B (NFIB), tumour suppressor gene, GBM subtype Received: November 30, 2015      Accepted: March 28, 2016      Published: April 13, 2016 ABSTRACT Glioblastoma (GBM) is an essentially incurable and rapidly fatal cancer, with few markers predicting a favourable prognosis. Here we report that the transcription factor NFIB is associated with significantly improved survival in GBM. NFIB expression correlates inversely with astrocytoma grade and is lowest in mesenchymal GBM. Ectopic expression of NFIB in low-passage, patient-derived classical and mesenchymal subtype GBM cells inhibits tumourigenesis. Ectopic NFIB expression activated phospho-STAT3 signalling only in classical and mesenchymal GBM cells, suggesting a mechanism through which NFIB may exert its context-dependent tumour suppressor activity. Finally, NFIB expression can be induced in GBM cells by drug treatment with beneficial effects.