Regulatory role of transcription factorHBP1in anticancer efficacy ofEGFRinhibitor erlotinib inHNSCC
Regulatory role of transcription factorHBP1in anticancer efficacy ofEGFRinhibitor erlotinib inHNSCC
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DOI：
10.1002/hed.26346
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发表时间：
2020-07-17
影响因子：
2.9
通讯作者：
Huang, Chun-Yin
中科院分区：
文献类型：
--
作者：
Chan, Chien-Yi;Chang, Chin-Ming;Huang, Chun-Yin
背景：表皮生长因子受体(EGFR)在头颈部鳞状细胞癌(HNSCC)中常被过度激活，但其下游调节因子尚未完全确定。在这里，我们研究了转录因子HBP1在EGFR抑制剂erlotinib对HNSCC的抗癌作用中的作用。方法采用流式细胞仪和Matrigel侵袭实验分别检测厄洛替尼和HBP1对细胞增殖和侵袭能力的影响。用口腔肿瘤标本评估EGFR和HBP1的表达水平与转移潜能之间的关系。结果厄洛替尼使细胞生长停滞于G1期，侵袭缓慢，HBP1和p27表达增加。HBP1基因敲除后，厄洛替尼效应减弱。对口腔肿瘤标本的分析表明，低HBP1/高EGFR状态可以预测转移潜能。结论我们的数据支持HBP1是HNSCC中EGFR靶向抑制物的重要介体。
Background Epidermal growth factor receptor (EGFR) is often hyperactivated in head and neck squamous cell carcinoma (HNSCC); however, its downstream mediators are not fully identified. Here, we investigate the role of transcription factor HBP1 in the anticancer efficacy of EGFR inhibitor erlotinib in HNSCC. Methods The effect of erlotinib and HBP1 on cell proliferation and invasion was examined by flow cytometric analysis and a Matrigel invasion assay, respectively. Oral tumor specimens were used to evaluate the association between the expression level of EGFR and HBP1, and metastatic potential. Results Erlotinib caused cell growth arrest in the G1 phase and sluggish invasion with a concomitant increase in HBP1 and p27 expression. The erlotinib effect was attenuated upon HBP1 knockdown. Analysis of oral tumor specimens revealed that the low HBP1/high EGFR status can predict metastatic potential. Conclusions Our data support HBP1 as a crucial mediator of EGFR-targeting inhibitors in HNSCC.