Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition



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.

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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
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