Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition.
Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition.
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DOI：
10.3892/or.2016.5189
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发表时间：
2016-12
期刊：
影响因子：
4.2
通讯作者：
Kawashiri S
中科院分区：
文献类型：
--
作者：
Kitahara H;Hirai M;Kato K;Bou-Gharios G;Nakamura H;Kawashiri S
抑制表皮生长因子受体(EGFR)信号已成为口腔鳞状细胞癌(OSCC)的一种新的治疗策略。此前，我们发现口腔鳞状细胞癌中EGFR表达的缺失与上皮-间充质转化(EMT)有关，并可能与抗EGFR单抗西妥昔单抗耐药有关。据报道，灯盏花素(一种微管抑制剂)通过触发间充质向上皮(MET)的转变，降低了乳腺癌的侵袭性和转移的可能性。在本研究中，我们评估了茜草素诱导的MET是否与口腔鳞癌耐药细胞系对西妥昔单抗的再增敏有关。用体外培养的人口腔鳞状细胞癌细胞系OSC-20、OSC-19和HOC313，观察淫羊藿苷对细胞增殖的抑制作用。这三种人类口腔鳞状细胞癌代表不同的EMT/MET状态。有趣的是，与其他细胞系相比，HOC313细胞(间充质表型)对eribuin高度敏感，并显著增强了西妥昔单抗对药物的抗增殖作用。灯盏花素还经历了MET相关的基因切换，导致了HOC313细胞的形态变化和EGFR的高表达，并取消了转化生长因子-β诱导的EMT基因表达特征。口腔鳞状细胞癌对西妥昔单抗的增敏作用可能是由于MET的诱导。以淫羊藿素和西妥昔单抗为基础的联合治疗方案有可能成为口腔鳞癌的一种新的治疗方案。
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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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
口腔鳞状细胞癌中表皮生长因子受体表达的丧失与侵袭性和上皮间质转化有关。
影响因子：
2.9
作者：
Kimura I;Kitahara H;Ooi K;Kato K;Noguchi N;Yoshizawa K;Nakamura H;Kawashiri S
通讯作者：
Kawashiri S
影响因子：
3.8
作者：
Haslehurst AM;Koti M;Dharsee M;Nuin P;Evans K;Geraci J;Childs T;Chen J;Li J;Weberpals J;Davey S;Squire J;Park PC;Feilotter H
通讯作者：
Feilotter H
影响因子：
2.9
作者：
Smith, Jennifer A.;Wilson, Leslie;Jordan, Mary Ann
通讯作者：
Jordan, Mary Ann
影响因子：
11.2
作者：
Kuznetsov, G;Towle, MJ;Littlefield, BA
通讯作者：
Littlefield, BA