The regulations of telomerase reverse transcriptase (TERT) in cancer

Abstract

Abnormal activation of telomerase occurs in most cancer types, which facilitates escaping from cell senescence. As the key component of telomerase, telomerase reverse transcriptase (TERT) is regulated by various regulation pathways. TERT gene changing in its promoter and phosphorylation respectively leads to TERT ectopic expression at the transcription and protein levels. The co-interacting factors play an important role in the regulation of TERT in different cancer types. In this review, we focus on the regulators of TERT and these downstream functions in cancer regulation. Determining the specific regulatory mechanism will help to facilitate the development of a cancer treatment strategy that targets telomerase and cancer cell senescence.

Pan-cancer experimental characteristic of human transcriptional patterns connected with telomerase reverse transcriptase (TERT) gene expression status

“…In over 80% of tumors, the increased TERT gene expression promotes abnormal telomerase activation and upregulated telomere maintenance mechanism ( Lee et al, 2016 ; Dratwa et al, 2020 ; Liu et al, 2024 ). In the context of cancer development, TERT serves as a critical factor by contributing to the maintenance of chromosomal stability through its role in preserving telomere length ( Colebatch et al, 2019 ).…”

“…However, the important roles of TERT in vital non-canonical processes other than telomerase activity should be also considered. For example, TERT can act as a modulator in NF-kB and Wnt/β-catenin signaling pathways, regulate gene expressions, proliferation, apoptosis, cell cycle, chromosomal rearrangements, epigenetic modifications ( Li and Tergaonkar, 2014 ; Dratwa et al, 2020 ; Liu et al, 2024 ). At the same time, in tumor cells with deficiencies in telomerase activity, telomere elongation can occur due to the telomerase-independent ALT pathway ( Zhao et al, 2019 ).…”