title: VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach.
abstract: OBJECTIVE
  To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer.
  
  
  METHODS
  Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to various HDACi were examined.
  
  
  RESULTS
  Significant effects on the regulation of the VEGF receptors were observed in response to HDACi. These were associated with decreased secretion of VEGF, decreased cellular proliferation and increased apoptosis which could not be rescued by addition of exogenous recombinant VEGF. Direct remodeling of the VEGFR1 and VEGFR2 promoters was observed. In contrast, HDACi treatments resulted in significant downregulation of the Neuropilin receptors.
  
  
  CONCLUSIONS
  Epigenetic targeting of the Neuropilin receptors may offer an effective treatment for lung cancer patients in the clinical setting.
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital & Trinity College Dublin, Dublin 8, Ireland.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Barr
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital & Trinity College Dublin, Dublin 8, Ireland.|Cancer & Ageing Research Program, Queensland University of Technology, Brisbane, Australia.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital & Trinity College Dublin, Dublin 8, Ireland.
authors.forename: Nael
authors.initials: N
authors.lastname: Al-Sarraf
authors.affiliation: Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital & Trinity College Dublin, Dublin 8, Ireland.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Gray
mesh_terms: D000107:Acetylation; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D042461:Vascular Endothelial Growth Factor A; C012589:trichostatin A; D000077337:Vorinostat; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: NSCLC; VEGF; epigenetics; histone deacetylase; histones; neuropilins; trichostatin-A