Telomerase: The Devil Inside.

Mukesh Kumar,Andre Lechel,Çagatay Güneş

doi:10.3390/genes7080043

Abstract

High telomerase activity is detected in nearly all human cancers but most human cells are devoid of telomerase activity. There is well-documented evidence that reactivation of telomerase occurs during cellular transformation. In humans, tumors can rely in reactivation of telomerase or originate in a telomerase positive stem/progenitor cell, or rely in alternative lengthening of telomeres, a telomerase-independent telomere-length maintenance mechanism. In this review, we will focus on the telomerase positive tumors. In this context, the recent findings that telomerase reverse transcriptase (TERT) promoter mutations represent the most common non-coding mutations in human cancer have flared up the long-standing discussion whether cancer originates from telomerase positive stem cells or telomerase reactivation is a final step in cellular transformation. Here, we will discuss the pros and cons of both concepts in the context of telomere length-dependent and telomere length-independent functions of telomerase. Together, these observations may provoke a re-evaluation of telomere and telomerase based therapies, both in telomerase inhibition for cancer therapy and telomerase activation for tissue regeneration and anti-ageing strategies.

Highlights

High telomerase activity is detected in most human cancers but most human cells are devoid of telomerase activity
Telomerase activity could be detected in the majority of human cancers [19], it is worth mentioning that about 10%–15% of human tumors were devoid of telomerase activity
High-throughput sequencing technologies have provided a new insight into the mechanisms of telomerase activation in cancer cells

Summary

Introduction

High telomerase activity is detected in most human cancers but most human cells are devoid of telomerase activity. 2. Regulatory Mechanisms Involved in TERT Gene Regulation in Normal and Tumor Cells occurrence of telomerase in human cancers motivated the development of telomerase inhibitors to Promoter whereas as a site of positive and negative regulation of hTERT gene expression depending on the proliferation of its counterpart Mad1 to the E-box sequences results in hTERT/telomerase downregulation [15,31,32].

Results

Conclusion