title: Nuclear factor one transcription factors as epigenetic regulators in cancer.
abstract: Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands imposed during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state. This stem cell-like phenotype primes tumour cells to react to external cues via the use of developmental pathways that facilitate changes in proliferation, migration and invasion. Because the dynamism of this stem cell-like state requires constant chromatin remodelling and rapid alterations at regulatory elements, it is of great therapeutic interest to identify the cell-intrinsic factors that confer these epigenetic changes that drive tumour progression. The nuclear factor one (NFI) family are transcription factors that play an important role in the development of many mammalian organ systems. While all four family members have been shown to act as either oncogenes or tumour suppressors across various cancer models, evidence has emerged implicating them as key epigenetic regulators during development and within tumours. Notably, NFIs have also been shown to regulate chromatin accessibility at distal regulatory elements that drive tumour cell dissemination and metastasis. Here we summarize the role of the NFIs in cancer, focusing largely on the potential mechanisms associated with chromatin remodelling and epigenetic modulation of gene expression.
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.|School of Biomedical Sciences, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD, Australia.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Fane
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Harris
authors.affiliation: School of Biomedical Sciences, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD, Australia.|Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Smith
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Michael
authors.identifier: 0000-0002-6759-2560
authors.initials: M
authors.lastname: Piper
mesh_terms: D018450:Disease Progression; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D051839:NFI Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D051839:NFI Transcription Factors; D020033:Protein Isoforms