The non-canonical functions of telomerase: to turn off or not to turn off

Abstract

Telomerase is perceived as an immortality enzyme that enables passing the Hayflick limit. Its main function is telomere restoration but only in a limited group of cells, including cancer cells. Since it is found in a vast majority of cancer cells, it became a natural target for cancer therapy. However, it has much more functions than just altering the metabolism of telomeres-it also reveals numerous so-called non-canonical functions. Thus, a question arises whether it is always beneficial to turn it off when planning a cancer strategy and considering potential side effects? The purpose of this review is to discuss some of the recent discoveries about telomere-independent functions of telomerase in the context of cancer therapy and potential side effects.

The Ribosome as a Missing Link in Prebiotic Evolution III: Over-Representation of tRNA- and rRNA-Like Sequences and Plieofunctionality of Ribosome-Related Molecules Argues for the Evolution of Primitive Genomes from Ribosomal RNA Modules

“…Even beyond that necessary evolutionary step, however, RNA polymerases have been found to play at least two additional roles in modern cells. One is gene silencing and transcription regulation [143,144], and the other is in myeloproliferation and hematopoiesis [145]. Given the wide range of functions taken on by other ribosome-related molecules, we predict that the polymerases will also be found to have additional functions.…”

TERT—Regulation and Roles in Cancer Formation

“…In the previous sections, we described TERT regulation and telomerase reactivation mechanisms that are involved in telomere maintenance. Telomere-related functions of TERT, also known as canonical, may likewise entail prevention of chromosome fusions ( 176 , 177 ). However, telomerase also has non-canonical (telomere-independent) roles ( Figure 1 ).…”

Anti-Cancer Immunotherapies Targeting Telomerase

“…In addition, TERT inhibition in cell culture led to telomere shortening, as well as cellular apoptosis and inhibition of cancer cell growth, thus providing additional evidence that telomerase is fundamental for cancer cell immortalization and tumor progression [8][9][10]. Besides the main canonical function related to telomere maintenance, telomerase displays different non-canonical activities including regulation of gene transcription, resistance to anti-growth signals, cell proliferation, β-catenin/MYC/NF-κB signaling, angiogenesis and epithelial-mesenchymal transitions (EMT), this latter being deeply implicated in migratory and invasive properties of cancer cells [11,12]. On the whole, this data indicates that telomerase, through its canonical and non-canonical functions, represents a central regulator of all of the hallmarks of cancer [12].…”