Telomerase: The Devil Inside

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.

Epigenetic perturbation driving asleep telomerase reverse transcriptase: Possible therapeutic avenues in carcinoma

“…A large number of papers describe that telomerase as ribonucleoprotein contains human telomerase RNA, human telomerase-associated protein, or dyskerin and hTERT. [3][4][5][6][7][8][12][13][14][15] In recent times, interests are rising to dissect out the contribution of DNA methylation, histone methylation, histone acetylation, and also non-coding RNAs in the epigenetically facilitated expression of hTERT. [25][26][27][28][31][32][33]44 Telomerase activity was detected in more than 95% of advanced stage breast cancers.…”

“…3,[12][13][14][15]62 In recent times, the activation of telomerase is considered as a mechanism to decelerate the genomic instability rate due to dysfunctional telomeres. 5,15,[19][20][21][22][23][24] The accepted fact is that telomerase may not push through the cancer progression, it may contribute toward the sustained growth of most advanced cancers 19,20 . Better prospects are viewed as precise and selective targeting of telomerase overexpression in carcinoma, but concomitantly sparing normal cell due to lack of telomerase expression.…”

“…[1][2][3][4][5][6][7][8] Hitherto, overexpression of hTERT is widely documented in more than 90% of cancer types including carcinoma. [4][5][6][7][8][9] The role of telomerase in the carcinoma-sustained growth and survival is overwhelmingly suggested. [4][5][6][7][8] In contrast, the telomere length is highly shortened in carcinoma, which is being stably maintained by the hTERT and associated telomeric proteins.…”

“…[4][5][6][7][8][9] The role of telomerase in the carcinoma-sustained growth and survival is overwhelmingly suggested. [4][5][6][7][8] In contrast, the telomere length is highly shortened in carcinoma, which is being stably maintained by the hTERT and associated telomeric proteins. 3,[10][11][12][13][14][15] In recent times, hTERT is associated to overcome cellular senescence and achieve cellular immortality in carcinoma.…”

“…[3][4][5] It is widely accepted that telomere loss could be a decisive factor in several cellular defects and altered tissue homeostasis. [3][4][5][6]16 However, a paradox scene is debated that genetically as well epigenetically dictated changes in the telomere length may swing in both ways either for curbing the cancer or helping progression. 5,15,[17][18][19][20][21][22][23][24] Although, there are healthy debate on the prospects of targeting telomere and telomerase as anticancer approaches, in addition looking into epigenetic regulation of hTERT is highly appreciated.…”