Blockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ERK signaling pathways

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.