机构：[1]Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, China.[2]Department of Oral and Maxillofacial Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.[3]Department of Stomatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Head and Neck squamous cell carcinomas (HNSCC), characterized by the high frequency of local recurrence and distant metastases, is mostly related to highly malignant and resistant to apoptosis, resulting in significant insensitivity to chemotherapy. Telomerase reverse transcriptase (TERT), as the catalytic subunit of telomerase, was implicated in the telomerase-mediated cellular transformation, proliferation, stemness and cell survival. Moreover, overexpression of human TERT (hTERT) is reported to be correlated with advanced invasive stage of the tumor progression and poor prognosis. Here, we show that hTERT potentially mediated the apoptotic resistance and blockade of telomerase reverse transcriptase could enhance chemosensitivity in head and neck cancers. Mechanistically, hTERT interacts with the phosphorylation of AKT and ERK to suppress the expression of p53, ultimately, leading to modulation of the cellular sensitivity to chemotherapy. Thus, these findings suggest that hTERT targeting could be an attractive approach in combination with conventional chemotherapies for patients suffering from chemoinsensitivity or refractory HNSCC.
基金：
National Natural Science Foundation of China (grant no.81072227)
第一作者机构：[1]Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, China.[2]Department of Oral and Maxillofacial Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Zhao Tengda,Hu Fengchun,Liu Xingguang,et al.Blockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ERK signaling pathways.[J].ONCOTARGET.2015,6(34):35908-35921.doi:10.18632/oncotarget.5468.
APA：
Zhao Tengda,Hu Fengchun,Liu Xingguang&Tao Qian.(2015).Blockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ERK signaling pathways..ONCOTARGET,6,(34)
MLA：
Zhao Tengda,et al."Blockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ERK signaling pathways.".ONCOTARGET 6..34(2015):35908-35921
