Abstract
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.
Highlights
Head and Neck squamous cell carcinomas (HNSCC), which arise in the oral cavity, larynx and pharynx, ranks as the sixth most prevalent cancer with approximately 500,000 new cases per year worldwide [1]
Our results suggest that the AKT/ERK-p53-bcl-2 axis might constitute a signaling cascade that mediates the antitumor treatment in HNSCC cells, and human TERT (hTERT) targeting could be an attractive approach in combination with conventional chemotherapies for patients suffering from chemoinsensitivity or refractory HNSCC
Further detection by Western blot was performed to find that hTERT expression was significantly upregulated in frequently utilized HNSCC cells compared with the immortalized normal keratinocyte cell line (NOK) (Figure 1A), suggesting hTERT might act as a strong promoter in malignant development of HNSCC
Summary
Head and Neck squamous cell carcinomas (HNSCC), which arise in the oral cavity, larynx and pharynx, ranks as the sixth most prevalent cancer with approximately 500,000 new cases per year worldwide [1]. HNSCC patients often present with advanced-stage tumors and the five-year survival rate is less than 50% [2, 3], this poor prognosis is mostly related to high malignancy and resistance to apoptosis, resulting in significant insensitivity to chemotherapy [4]. Telomerase is an enzyme best known for its role in telomere maintenance [5]. Several studies have demonstrated that human TERT (hTERT) was implicated in the telomerase-mediated cellular transformation [6], proliferation [7], stemness [8] and cell survival [9]. Overexpression of hTERT is reported to be correlated with advanced invasive stage of the tumor progression and poor prognosis [13,14,15,16]
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