Implications of telomere‐independent activities of telomerase reverse transcriptase in human cancer

Abstract

Telomerase plays a pivotal role in the pathology of cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Experimental data from genetically modified mice and human premature aging diseases clearly indicate that intact telomere function is crucial for cell proliferation and survival, whereas dysfunctional telomeres can lead to either cancer or aging pathologies, depending on the integrity of the cellular stress response pathways. The canonical function of telomerase reverse transcriptase is the synthesis of telomeric DNA repeats and the maintenance of telomere length. However, accumulating evidence indicates that telomerase reverse transcriptase may also exert some fundamental biological functions independently of its enzymatic activity in telomere maintenance. More recent studies have demonstrated that telomerase reverse transcriptase can act as a transcriptional modulator in the nucleus and exhibits RNA-dependent RNA polymerase activity in the mitochondria. Telomerase activation may have both telomere-dependent and telomereindependent implications for tumor progression. Many excellent reviews have described critical roles of telomere and telomerase in human cancer; this minireview will focus on the role of telomerase in cancer progression, with a special emphasis on the nontelomeric function of telomerase.

Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions

“…Moreover, the binding of telomerase to NF-kB-dependent genes and expression stimulation was markedly enhanced and rapidly activated by the addition of TNF-a. A recent report, however, showed that TERT can function independent of its enzymatic function to regulate the NF-kB-dependent transcription 37 . This discrepancy requires clarification in future studies.…”

Arsenic trioxide suppresses transcription of hTERT through down-regulation of multiple transcription factors in HL-60 leukemia cells

“…Telomeres play a crucial role in maintaining genome stability and in controlling the replication potential in somatic cells (Ding et al, 2013). In normal human somatic cells, telomeres shorten with each cell division, contributing to limited cell replications.…”

“…In normal human somatic cells, telomeres shorten with each cell division, contributing to limited cell replications. However, many cancer cells develop a mechanism to escape from this limitation by overexpressing telomerase, an enzyme that maintains the telomere length (Ding et al, 2013;Holysz et al, 2013;Xu et al, 2013). Telomerase constitutes three major proteins, and hTERT is the major determinant of the telomerase activity.…”

Study of <b><i>hTERT</i></b> and Histone 3 Mutations in Medulloblastoma

“…Although telomerase is normally silenced in somatic cells, it is active in male germ cells, activated lymphocytes, stem cell populations and during development [4][5][6] . In the large majority of human cancers, abnormal telomerase reactivation is observed, leading to telomere maintenance and limitless proliferative potential [7][8][9] .…”