Human Telomerase Reverse Transcriptase (hTERT) Is a Novel Target of the Wnt/β-Catenin Pathway in Human Cancer

Abstract

Background: Telomerase up-regulation is found in about 90% of human cancer specimens and contributes actively to carcinogenesis. Results: ␤-Catenin⅐TCF4 plays an important role in telomerase activation. Conclusion: hTERT is a direct transcriptional target of the Wnt/␤-catenin pathway. Significance: Identifying the function of the Wnt/␤-catenin pathway in telomerase regulation provides better insight into the role of Wnt pathway in carcinogenesis.

Noncanonical Functions of Telomerase: Implications in Telomerase-Targeted Cancer Therapies

“…As such, the role of telomerase on Wnt signaling should not be dismissed completely but rather, be viewed as one that is context dependent and especially relevant in cancers in which multiple signaling pathways such as NF-kB and Wnt are perturbed concurrently. In addition, the finding that Wnt/b-catenin signaling can in turn regulate telomerase transcriptionally in embryonic stem cells and human cancer cells (14,15) further fuels the notion of a feed-forward regulatory cycle that sustains telomerase activity and amplifies oncogenic signaling mechanisms concurrently.…”

“…However, during human tumorigenesis, telomerase is often reactivated via transcriptional upregulation of TERT. The expression of telomerase can be stimulated by transcription factors/coregulators that are well documented for their cancer-promoting roles, such as c-Myc (12), NF-kB (13) and b-catenin (14,15). Telomerase upregulation enables rapidly proliferating cancer cells to bypass checkpoint signaling pathways that are activated during critical telomere shortening to induce cellular senescence and cell death.…”

Live-cell imaging reveals the dynamics and function of single-telomere TERRA molecules in cancer cells

“…This feature would favour the imaging of TERRA transcripts localization at telomeres. AGS cells are telomerase positive cells harbouring a WT p53 gene [30,31]. …”

Comprimento telomérico no sistema nervoso central de um modelo de doença de Alzheimer tratado com lí­tio

“…O tamanho dos telômeros também é inversamente proporcional aos níveis de fator de necrose tumoral α, sugerindo o envolvimento do sistema imune na neuropatologia da DA (PANOSSIAN et al, 2003). Zhang e colaboradores (2003) …”

“…As análises individuais são descritas nos tópicos seguintes. O lítio pode ter um importante papel na modulação da telomerase, uma enzima ribonucleoproteica responsável pela manutenção do comprimento telomérico (ZHANG et al, 2012;OZTURK;LI;TERGAONKAR, 2017). A TERT é a subunidade catalítica que regula e limita a atividade da telomerase (HARTWIG et al, 2012;OZTURK;LI;TERGAONKAR, 2017).…”