Non-canonical roles of canonical telomere binding proteins in cancers

被引:28
|
作者
Akincilar, Semih Can [1 ]
Chan, Claire Hian Tzer [1 ]
Ng, Qin Feng [1 ]
Fidan, Kerem [1 ]
Tergaonkar, Vinay [1 ,2 ]
机构
[1] ASTAR, Inst Mol & Cell Biol IMCB, Lab NFB Signaling, Div Canc Genet & Therapeut, 61,Biopolis Dr, Singapore 138673, Singapore
[2] Natl Univ Singapore, Dept Pathol, Yong Loo Lin Sch Med, Singapore 117593, Singapore
基金
英国医学研究理事会;
关键词
Telomerase; Shelterin; Telomere; Cancer; TERT;
D O I
10.1007/s00018-021-03783-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reactivation of telomerase is a major hallmark observed in 90% of all cancers. Yet paradoxically, enhanced telomerase activity does not correlate with telomere length and cancers often possess short telomeres; suggestive of supplementary non-canonical roles that telomerase might play in the development of cancer. Moreover, studies have shown that aberrant expression of shelterin proteins coupled with their release from shortening telomeres can further promote cancer by mechanisms independent of their telomeric role. While targeting telomerase activity appears to be an attractive therapeutic option, this approach has failed in clinical trials due to undesirable cytotoxic effects on stem cells. To circumvent this concern, an alternative strategy could be to target the molecules involved in the non-canonical functions of telomeric proteins. In this review, we will focus on emerging evidence that has demonstrated the non-canonical roles of telomeric proteins and their impact on tumorigenesis. Furthermore, we aim to address current knowledge gaps in telomeric protein functions and propose future research approaches that can be undertaken to achieve this.
引用
收藏
页码:4235 / 4257
页数:23
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