Kumar Naveen, Sethi Gautam
Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore, 138673, Singapore.
Department of Pharmacology and NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
Cancer Lett. 2023 Dec 1;578:216459. doi: 10.1016/j.canlet.2023.216459. Epub 2023 Oct 19.
Transformed cells must acquire specific characteristics to be malignant. Weinberg and Hanahan characterize these characteristics as cancer hallmarks. Though these features are independently driven, substantial signaling crosstalk in transformed cells efficiently promotes these feature acquisitions. Telomerase is an enzyme complex that maintains telomere length. However, its main component, Telomere reverse transcriptase (TERT), has been found to interact with various signaling molecules like cMYC, NF-kB, BRG1 and cooperate in transcription and metabolic reprogramming, acting as a strong proponent of malignant features such as cell death resistance, sustained proliferation, angiogenesis activation, and metastasis, among others. It allows cells to avoid replicative senescence and achieve endless replicative potential. This review summarizes both the canonical and noncanonical functions of TERT and discusses how they promote cancer hallmarks. Understanding the role of Telomerase in promoting cancer hallmarks provides vital insight into the underlying mechanism of cancer genesis and progression and telomerase intervention as a possible therapeutic target for cancer treatment. More investigation into the precise molecular mechanisms of telomerase-mediated impacts on cancer hallmarks will contribute to developing more focused and customized cancer treatment methods.
转化细胞必须获得特定特征才能具有恶性。温伯格和哈纳汉将这些特征描述为癌症标志。尽管这些特征是由独立驱动的，但转化细胞中大量的信号串扰有效地促进了这些特征的获得。端粒酶是一种维持端粒长度的酶复合物。然而，其主要成分端粒逆转录酶（TERT）已被发现与多种信号分子如cMYC、NF-κB、BRG1相互作用，并在转录和代谢重编程中协同作用，作为细胞抗死亡、持续增殖、血管生成激活和转移等恶性特征的有力支持者。它使细胞能够避免复制性衰老并实现无限的复制潜能。本综述总结了TERT的经典和非经典功能，并讨论了它们如何促进癌症标志。了解端粒酶在促进癌症标志中的作用，为深入了解癌症发生和发展的潜在机制以及将端粒酶干预作为癌症治疗的可能靶点提供了重要见解。对端粒酶介导的对癌症标志影响的精确分子机制进行更多研究，将有助于开发更有针对性和个性化的癌症治疗方法。
