Open Access

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

  • Authors:
    • Hiroko Kitahara
    • Mariko Hirai
    • Koroku Kato
    • George Bou-Gharios
    • Hiroyuki Nakamura
    • Shuichi Kawashiri
  • View Affiliations

  • Published online on: October 21, 2016     https://doi.org/10.3892/or.2016.5189
  • Pages: 3139-3144
  • Copyright: © Kitahara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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December-2016
Volume 36 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kitahara H, Hirai M, Kato K, Bou-Gharios G, Nakamura H and Kawashiri S: Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition. Oncol Rep 36: 3139-3144, 2016
APA
Kitahara, H., Hirai, M., Kato, K., Bou-Gharios, G., Nakamura, H., & Kawashiri, S. (2016). Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition. Oncology Reports, 36, 3139-3144. https://doi.org/10.3892/or.2016.5189
MLA
Kitahara, H., Hirai, M., Kato, K., Bou-Gharios, G., Nakamura, H., Kawashiri, S."Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition". Oncology Reports 36.6 (2016): 3139-3144.
Chicago
Kitahara, H., Hirai, M., Kato, K., Bou-Gharios, G., Nakamura, H., Kawashiri, S."Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition". Oncology Reports 36, no. 6 (2016): 3139-3144. https://doi.org/10.3892/or.2016.5189