title: Aurora B expression modulates paclitaxel response in non-small cell lung cancer.
abstract: BACKGROUND
  Taxanes are mitotic poisons widely used in the treatment of non-small cell lung cancer (NSCLC), however, little is known about potential molecular modulators of response to these compounds. Aurora B (AURKB) is a critical regulator of the mitotic spindle assembly, previously shown overexpressed in NSCLC. Here we investigated the hypothesis that AURKB expression modulates the efficacy of taxanes in NSCLC cells.
  
  
  METHODS
  AURKB mRNA expression was determined by qPCR in 132 frozen NSCLC tissues and nine NSCLC cell lines. Aurora B expression was knocked down in cell lines using multiple shRNA constructs. Barasertib was used to specifically inhibit AURKB activity, determined by the level of H3S10 phosphorylation.
  
  
  RESULTS
  Frequent AURKB mRNA upregulation was observed in NSCLC tissues (P<0.0001), being more prominent in squamous carcinomas (P<0.0001). Aurora B expression in cell lines strongly correlated with sensitivity to both docetaxel (P=0.004) and paclitaxel (P=0.007). Aurora B knockdown derivatives consistently showed a dose-dependent association between low-AURKB expression and resistance to paclitaxel. Specific chemical inhibition of Aurora B activity also demonstrated a strong dose-dependent efficiency in triggering paclitaxel resistance.
  
  
  CONCLUSIONS
  Aurora B activity is an important modulator of taxane response in NSCLC cells. This may lead to further insights into taxane sensitivity of NSCLC tumours.
authors.affiliation: Roy Castle Lung Cancer ResearchProgramme, Department of Molecular and Clinical Cancer Medicine, Instituteof Translational Medicine, University of Liverpool,Liverpool, UK.|Department of Biology, Collage ofScience, University of Baghdad, Baghdad,Iraq.
authors.forename: Ahmed Sk
authors.initials: AS
authors.lastname: Al-Khafaji
authors.affiliation: Roy Castle Lung Cancer ResearchProgramme, Department of Molecular and Clinical Cancer Medicine, Instituteof Translational Medicine, University of Liverpool,Liverpool, UK.
authors.forename: Michael Pa
authors.initials: MP
authors.lastname: Davies
authors.affiliation: Mersey Head and Neck OncologyResearch Group, Department of Molecular and Clinical Cancer Medicine,Institute of Translational Medicine, University of Liverpool,Liverpool, UK.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Risk
authors.affiliation: Roy Castle Lung Cancer ResearchProgramme, Department of Molecular and Clinical Cancer Medicine, Instituteof Translational Medicine, University of Liverpool,Liverpool, UK.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Marcus
authors.affiliation: Department of Molecular Biology andGenetics, Democritus University of Thrace,Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Koffa
authors.affiliation: Roy Castle Lung Cancer ResearchProgramme, Department of Molecular and Clinical Cancer Medicine, Instituteof Translational Medicine, University of Liverpool,Liverpool, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Gosney
authors.affiliation: Mersey Head and Neck OncologyResearch Group, Department of Molecular and Clinical Cancer Medicine,Institute of Translational Medicine, University of Liverpool,Liverpool, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Shaw
authors.affiliation: Roy Castle Lung Cancer ResearchProgramme, Department of Molecular and Clinical Cancer Medicine, Instituteof Translational Medicine, University of Liverpool,Liverpool, UK.
authors.forename: John K
authors.initials: JK
authors.lastname: Field
authors.affiliation: Roy Castle Lung Cancer ResearchProgramme, Department of Molecular and Clinical Cancer Medicine, Instituteof Translational Medicine, University of Liverpool,Liverpool, UK.
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Liloglou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D064107:Aurora Kinase B / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000494:pharmacology; D017239:Paclitaxel / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D000972:Antineoplastic Agents, Phytogenic; D010755:Organophosphates; D011799:Quinazolines; C576921:AURKB protein, human; D064107:Aurora Kinase B; D017239:Paclitaxel