Regulation of telomerase activity by apparently opposing elements

Liu, Junping; Chen, Shi‐Ming; Cong, Yu Sheng; Nicholls, Craig; Zhou, Shu Feng; Tao, Ze; Li, He

doi:10.1016/j.arr.2010.03.002

Cited by 45 publications

(36 citation statements)

References 155 publications

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“…[11][12][13][14][15] Telomerase is a RNA-dependent DNA polymerase that elongates the 5 0 -TTAGGG-3 0 telomeric DNA. 16 Most normal human somatic cells lack telomerase activity because of the tight transcriptional repression of its rate-limiting, catalytic component telomerase reverse transcriptase (hTERT) gene. 16,17 It is well established that stabilization of telomere length is required for transformed cells to achieve infinite proliferation potential during oncogenesis, and activation of telomerase/induction of hTERT expression to maintain telomere sizes is a critical step in transformation.…”

Section: Introductionmentioning

confidence: 99%

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Telomerase reverse transcriptase promotes epithelial–mesenchymal transition and stem cell-like traits in cancer cells

et al. 2012

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Telomerase activation through induction of telomerase reverse transcriptase (hTERT) contributes to malignant transformation by stabilizing telomeres. Clinical studies demonstrate that higher hTERT expression is associated with cancer progression and poor outcomes, but the underlying mechanism is unclear. Because epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are key factors in cancer metastasis and relapse, and hTERT has been shown to exhibit multiple biological activities independently of its telomere-lengthening function, we address a potential role of hTERT in EMT and CSCs using gastric cancer (GC) as a model. hTERT overexpression promotes, whereas its inhibition suppresses, EMT and stemness of GC cells, respectively. Transforming growth factor (TGF)-β1 and β-catenin-mediated EMT was abolished by small interfering RNA depletion of hTERT expression. hTERT interacts with β-catenin, enhances its nuclear localization and transcriptional activity, and occupies the β-catenin target vimentin promoter. All these hTERT effects were independent of its telomere-lengthening function or telomerase activity. hTERT and EMT marker expression correlates positively in GC samples. Mouse experiments demonstrate the in vivo stimulation of hTERT on cancer cell colonization. Collectively, hTERT stimulates EMT and induces stemness of cancer cells, thereby promoting cancer metastasis and recurrence. Thus, targeting hTERT may prevent cancer progression by inhibiting EMT and CSCs.

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Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14][15] Telomerase is a RNA-dependent DNA polymerase that elongates the 5 0 -TTAGGG-3 0 telomeric DNA. 16 Most normal human …”

mentioning

confidence: 99%

Telomerase reverse transcriptase promotes epithelial–mesenchymal transition and stem cell-like traits in cancer cells

et al. 2012

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“…Regulation of TERT is achieved at many levels, with gene expression, alternative splicing, protein folding, post-translational modification and interaction partners all influencing the expression and activity of TERT (Liu et al, 2010). The following will refer to the regulation of TERT in humans unless otherwise stated.…”

Section: Regulation Of Telomerasementioning

confidence: 99%

“…Furthermore, inhibition of telomerase activity in telomerase-positive cancer cells results in cell death and tumor growth inhibition (Hahn et al, 1999;Herbert et al, 1999;Zhang et al, 1999;Cassar et al, 2008). This highlights the critical role of telomerase in facilitating and enabling cancer cell proliferation and has led to the development of several telomerase inhibitors that are currently being investigated as candidate anti-cancer drugs (reviewed in (Harley, 2008;Liu et al, 2010)). …”

Section: Introductionmentioning

confidence: 99%

Molecular regulation of telomerase activity in aging

Nicholls

Wang

et al. 2011

Protein Cell

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The process of aging is mitigated by the maintenance and repair of chromosome ends (telomeres), resulting in extended lifespan. This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase (TERT), which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy. Underpinning increased cell proliferation, telomerase is also a key factor in facilitating cancer cell immortalization. The review focuses on aspects of hormonal regulations of telomerase, and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels. In addition, the basic structure and function of two key telomerase enzyme components-the catalytic subunit TERT and the template RNA (TERC) are discussed briefly.

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“…For example, an inverse association has been observed between C-reactive protein and telomere length in a sample of older adults. 70 Pro-inflammatory cytokines have also been shown to regulate telomerase activity in cultured cells, 71 which may influence telomere length.…”

Section: Potential Mechanisms Mediating the Relationship Between Deprmentioning

confidence: 99%

Exploring the link between depression and accelerated cellular aging: telomeres hold the key

Yu¹,

Woo²

2015

RRBC

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Accumulating evidence suggests that telomeres may be a marker for biological aging and telomere length may be affected by multifactorial influences, including cumulative exposure to depression. Associations with telomere length have been reported for major depressive disorder, lifetime duration of depression, higher depression severity, and history of depression. The exact underling mechanisms for these associations have yet to be fully elucidated; however, oxidative stress, chronic inflammation, dysregulated hypothalamus-pituitary-adrenal axis, and altered cortisol levels may be important biochemical mediators. These mediators could also be influenced by psychological stress, unhealthy lifestyle behaviors, or other potential factors, such as childhood abuse, post-traumatic stress disorder, and anxiety that are commonly associated with depression. As such, stress reduction and lifestyle interventions that may affect the telomere maintenance system should be considered for individuals with depression.

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Regulation of telomerase activity by apparently opposing elements

Cited by 45 publications

References 155 publications

Telomerase reverse transcriptase promotes epithelial–mesenchymal transition and stem cell-like traits in cancer cells

Telomerase reverse transcriptase promotes epithelial–mesenchymal transition and stem cell-like traits in cancer cells

Molecular regulation of telomerase activity in aging

Exploring the link between depression and accelerated cellular aging: telomeres hold the key

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