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

• Kawashiri, Shuichi

抄録

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 antiproliferative 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-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.

Embargo Period 6 months

収録刊行物

• Oncology Reports

  Oncology Reports 36 (6), 3139-3144, 2016-12-01

  Spandidos Publications

キーワード

• Cetuximab
• Epidermal growth factor receptor
• Epithelial-mesenchymal transition
• Eribulin
• Oral cancer

詳細情報

• CRID: 1050845760881227520
• NII論文ID: 120005973603
• NII書誌ID: AA11016405
• ISSN: 1021335X
• Web Site: http://hdl.handle.net/2297/46748
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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  • CiNii Articles