Telomeres and telomerase in oncogenesis (Review)

Abstract

Telomeres are located at the ends of chromosomes and protect them from degradation. Suppressing the activity of telomerase, a telomere-synthesizing enzyme, and maintaining short telomeres is a protective mechanism against cancer in humans. In most human somatic cells, the expression of telomerase reverse transcriptase (TERT) is repressed and telomerase activity is inhibited. This leads to the progressive shortening of telomeres and inhibition of cell growth in a process called replicative senescence. Most types of primary cancer exhibit telomerase activation, which allows uncontrolled cell proliferation. Previous research indicates that TERT activation also affects cancer development through activities other than the canonical function of mediating telomere elongation. Recent studies have improved the understanding of the structure and function of telomeres and telomerase as well as key mechanisms underlying the activation of TERT and its role in oncogenesis. These advances led to a search for drugs that inhibit telomerase as a target for cancer therapy. The present review article summarizes the organization and function of telomeres, their role in carcinogenesis, and advances in telomerase-targeted therapy.

hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

“…It has been reported that hTERT and telomerase activity play a vital role in cell immortalization [32], transformation [33], proliferation [34] and metastasis [35]. A previous study indicated that hTERT could affect cancer development via activity not involving telomere elongation [36]. In the present study, our data provide strong evidence suggesting that hTERT plays a signi cant role in promoting CRC cell proliferation and migration.…”

TERT—Regulation and Roles in Cancer Formation

“…This mutation leads to increased GABPA-GABPB complex formation and activation of TERT expression ( 29 , 49 ). Co-existence of TERTp mutation and V600E is associated with poor prognosis in patients with thyroid cancer, particularly papillary thyroid cancer ( 8 , 50 ). Fibroblast growth factor receptor 3 ( FGFR3 ) is another example of genetic alterations interacting with TERTp .…”

“…It is an RNA sequence, which functions as a template for synthesis of telomeres by TERT. These two main components of telomerase are accompanied by a host of auxiliary proteins, including dyskerin (DKC1), telomerase Cajal body protein 1 (TCAB1), non-histone chromosome protein 2 (NHP2), nucleolar protein 10 (NOP10), glycine arginine rich 1 (GAR1), heat shock protein 90 (HSP90) and serine and arginine rich splicing factor 11 (SRSF11) ( 8 ). This complex is essential for maintaining telomere homeostasis, which is crucial in regulation of aging and cancer development ( 9 ).…”

PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex

“…The telomeric sequence displays a pronounced polymorphism and several structures have been characterized, predominantly the hybrid mixture and antiparallel and parallel topologies [ 21 , 22 , 23 , 24 ]. Moreover, this sequence is closely related to the catalytic activity of ribonucleoprotein telomerase, abnormally significant in many types of human tumors [ 25 ]. Therefore, both telomeres and telomerase have become interesting targets for the discovery of novel anticancer agents [ 26 ].…”