Hypoxia induces TFE3 expression in head and neck squamous cell carcinoma.
Hypoxia induces TFE3 expression in head and neck squamous cell carcinoma.
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缺氧诱导头颈部鳞状细胞癌中 TFE3 的表达。
DOI：
10.18632/oncotarget.7309
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发表时间：
2016-03-08
期刊：
影响因子：
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通讯作者：
Zhang L
中科院分区：
文献类型：
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作者：
Sun ZJ;Yu GT;Huang CF;Bu LL;Liu JF;Ma SR;Zhang WF;Liu B;Zhang L
为了评估转录因子μE3（TFE 3）在头颈部鳞状细胞癌（HNSCC）肿瘤发生中的作用，研究了人HNSCC组织阵列中TFE 3的表达。对新辅助诱导化疗（多西他赛、顺铂和氟尿嘧啶，TPF）的人HNSCC组织和来自转基因小鼠模型的小鼠HNSCC组织进行TFE 3表达和缺氧途径的评价。在体外和体内分析EGF/EGFR介导的缺氧在TFE 3核表达中的作用。TFE 3在人口腔鳞状细胞癌组织中的表达高于正常口腔黏膜组织。TFE 3的高表达与HIF-1α、派-1和EGFR相关，提示HNSCC组织中缺氧通路的激活。此外，在顺铂为基础的化疗后，HNSCC中观察到TFE 3表达升高，并且TFE 3高表达可能指示对TPF诱导化疗的不良反应。此外，在转基因小鼠HNSCC模型的HNSCC中观察到TFE 3增加的类似变化。缺氧培养的人HNSCC细胞系增加了TFE 3的表达，这促进了细胞在缺氧条件下的存活。西妥昔单抗对EGFR的抑制作用可减弱HNSCC细胞系和转基因小鼠HNSCC模型中缺氧诱导的TFE 3。提示TFE 3是HNSCC缺氧诱导的重要转录因子。TFE 3通过抑制EGFR表达，可作为一个持久的治疗靶点。
To assess the role of transcription factor μE3 (TFE3) in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC), human HNSCC tissue arrays were investigated for TFE3 expression. Human HNSCC tissues with neoadjuvant inductive chemotherapey (docetaxel, cisplatin and fluorouracil, TPF) and mice HNSCC tissues from transgenic mice model were evaluated for TFE3 expression and the hypoxia pathway. The roles of EGF/EGFR mediated hypoxia in TFE3 nuclear expression were analyzed in vitro and in vivo. TFE3 expression was higher in human HNSCC tissues compared with that in normal oral mucosa. Moreover, high TFE3 expression was related to HIF-1α, PAI-1, and EGFR, which demonstrated the activation of the hypoxia pathway in HNSCC tissues. Furthermore, elevated TFE3 expression was observed in HNSCC after cisplatin-based chemotherapy, and high TFE3 expression may indicate poor response to TPF inductive chemotherapy. Furthermore, similar changes with increased TFE3 were observed in HNSCC of the transgenic mouse HNSCC model. Hypoxic culture in the human HNSCC cell line increased TFE3 expression, which promoted cell survival under hypoxia. EGFR inhibiton by cetuximab could attenuate hypoxia-induced TFE3 in the HNSCC cell line and transgenic mouse HNSCC model. These findings indicated that TFE3 was an important hypoxia-induced transcriptional factor in HNSCC. TFE3 could be regarded as a durgable therapeutic oncotarget by EGFR inhibition.