Kitahara, Hiroko, Hirai, Mariko, Kato, Koroku, Bou-Gharios, George, Nakamura, Hiroyuki and Kawashiri, Shuichi
(2016)
Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition.
ONCOLOGY REPORTS, 36 (6).
pp. 3139-3144.
Text
Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition.pdf - Published version Download (513kB) |
Abstract
Inhibition of epidermal growth factor receptor (EGFR) signalling has emerged as a new treatment strategy for oral squamous cell carcinoma (OSCC). Previously, we found that loss of EGFR expression in OSCC was associated with epithelial-mesenchymal transition (EMT), and may have functional implications with regard to resistance to cetuximab, a monoclonal anti-EGFR antibody. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering mesenchymal‑to‑epithelial (MET) transition. In the present study we evaluated whether eribulin-induced MET was associated with re-sensitization of resistant OSCC cell lines to cetuximab. In vitro antiproliferative activities were determined in three human OSCC lines (OSC-20, OSC-19 and HOC313) treated with eribulin. These three human OSCC represented different EMT/MET states. Interestingly, HOC313 cells (mesenchymal phenotype) were highly sensitive to eribulin in comparison with other cell lines, and significantly enhanced the anti-proliferative effect of cetuximab in response to the drug. Eribulin also underwent a MET-associated gene switch that resulted in morphological changes and high EGFR expression in HOC313 cells, and abrogated a TGF-β-induced EMT gene expression signature. Eribulin-dependent sensitization of OSCC to cetuximab is likely due to induction of MET. Combination therapies based on eribulin and cetuximab have potential as a novel treatment regimen in OSCC.
Item Type: | Article |
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Uncontrolled Keywords: | eribulin, oral cancer, epidermal growth factor receptor, cetuximab, epithelial-mesenchymal transition |
Depositing User: | Symplectic Admin |
Date Deposited: | 11 Apr 2017 06:23 |
Last Modified: | 19 Jan 2023 07:06 |
DOI: | 10.3892/or.2016.5189 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3006934 |