Aurora B expression modulates paclitaxel response in non-small cell lung cancer.



Al-Khafaji, AS, Davies, MP ORCID: 0000-0002-7609-4977, Risk, JM ORCID: 0000-0002-8770-7783, Marcus, MW, Koffa, M, Gosney, JR, Shaw, RJ ORCID: 0000-0002-5157-4042, Field, JK ORCID: 0000-0003-3951-6365 and Liloglou, T ORCID: 0000-0003-0460-1404
(2017) Aurora B expression modulates paclitaxel response in non-small cell lung cancer. British journal of cancer, 116 (05). 592 - 599.

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Abstract

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.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.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.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.

Item Type: Article
Uncontrolled Keywords: taxanes, resistance, lung cancer, aurora, barasertib
Depositing User: Symplectic Admin
Date Deposited: 09 Feb 2017 13:04
Last Modified: 01 Aug 2020 07:10
DOI: 10.1038/bjc.2016.453
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3005630