Regulation of Telomerase in Normal and Cancer Stem Cells

Dysfunction of telomerase, a ribonucleoprotein that repairs telomeres, can lead to cancer. Telomerase activity varies between different types of cells and is abnormally high in cancer stem cells due to changes in the regulation of telomerase, resulting in the cancer stem cells acquiring replicative immortality capacity. Cancer stem cells have stemness properties and play an important role in tumour growth, tumour recurrence and cancer metastasis. Peer-reviewed articles from publicly available databases published over the past twenty years were included in this study. During early tumourigenesis, non-coding mutations in the TERT gene promotor lead to the binding of the GABPA-GABPB tetramer to an extra ETS binding site that does not exist in normal cells, increasing TERT transcription. Various factors, such as sex hormones, stress hormones and growth factors are also involved in telomerase regulation, and their effect on telomerase activities varies. Telomerase activity can be used as a potential biomarker of cancer stem cells. Telomerase inhibitors and immunotherapies are developed to be used in cancer therapy. Challenges such as difficulty in targeting the tumour exist, and there are limitations to using telomerase as a cancer therapeutic target. This paper focuses on the regulation of telomerase in normal and cancer stem cells.