Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma.
Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma.
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端粒酶逆转录酶和β-连环蛋白在肝细胞癌中相互作用的研究
DOI：
10.3390/cancers13164202
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发表时间：
2021-08-20
期刊：
影响因子：
5.2
通讯作者：
Evason KJ
中科院分区：
文献类型：
--
作者：
Kotiyal S;Evason KJ
肝癌是人类最致命的癌症之一。肝癌中最常见的两种分子畸变是：（1）编码β-连环蛋白（CTNNB 1）的基因激活突变;（2）端粒酶逆转录酶（TERT）启动子突变。在这里，我们回顾了最近的研究结果，关于端粒酶逆转录酶和β-连环蛋白之间的相互作用，以更好地了解他们在肝癌中的作用。肝细胞癌（HCC）是人类最致命的癌症之一。端粒酶逆转录酶（TERT）启动子（TERTp）和编码β-连环蛋白的CTNNB 1基因的激活突变在HCC中广泛存在（分别为~50%和~ 30%）。预测TERTp突变增加TERT转录和端粒酶活性。本文就端粒酶逆转录酶和β-catenin在肝细胞癌中的作用及其相互作用的研究进展作一综述。TERT通过其典型和非典型功能对肿瘤发生具有矛盾的作用。作为祖细胞和干细胞增殖和分化的关键调节因子，活化的β-连环蛋白驱动HCC;然而，抑制内源性β-连环蛋白也可以具有促肿瘤作用。临床研究显示，TERTp和CTNNB 1突变在HCC中具有显著的一致性。在干细胞中，TERT作为β-连环蛋白转录复合物中的辅因子驱动WNT/β-连环蛋白靶基因的表达，并且β-连环蛋白可以结合TERTp以驱动其转录。一些研究已经检测了体内肝癌中TERT和β-catenin之间的潜在相互作用，他们的结果表明这两个基因的共表达促进了肝癌的发生。需要进一步研究脊椎动物模型，以更好地了解TERT和β-catenin如何影响肝癌发生。
Liver cancer is one of the deadliest human cancers. Two of the most common molecular aberrations in liver cancer are: (1) activating mutations in the gene encoding β-catenin (CTNNB1); and (2) promoter mutations in telomerase reverse transcriptase (TERT). Here, we review recent findings regarding the interplay between TERT and β-catenin in order to better understand their role in liver cancer. Hepatocellular carcinoma (HCC) is one of the deadliest human cancers. Activating mutations in the telomerase reverse transcriptase (TERT) promoter (TERTp) and CTNNB1 gene encoding β-catenin are widespread in HCC (~50% and ~30%, respectively). TERTp mutations are predicted to increase TERT transcription and telomerase activity. This review focuses on exploring the role of TERT and β-catenin in HCC and the current findings regarding their interplay. TERT can have contradictory effects on tumorigenesis via both its canonical and non-canonical functions. As a critical regulator of proliferation and differentiation in progenitor and stem cells, activated β-catenin drives HCC; however, inhibiting endogenous β-catenin can also have pro-tumor effects. Clinical studies revealed a significant concordance between TERTp and CTNNB1 mutations in HCC. In stem cells, TERT acts as a co-factor in β-catenin transcriptional complexes driving the expression of WNT/β-catenin target genes, and β-catenin can bind to the TERTp to drive its transcription. A few studies have examined potential interactions between TERT and β-catenin in HCC in vivo, and their results suggest that the coexpression of these two genes promotes hepatocarcinogenesis. Further studies are required with vertebrate models to better understand how TERT and β-catenin influence hepatocarcinogenesis.
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影响因子：
--
作者：
Gao C;Wang Y;Broaddus R;Sun L;Xue F;Zhang W
通讯作者：
Zhang W
影响因子：
5.3
作者：
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
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Cancer Genome Atlas Research Network
影响因子：
3.5
作者：
Gaspar TB;Sá A;Lopes JM;Sobrinho-Simões M;Soares P;Vinagre J
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影响因子：
4.5
作者：
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通讯作者：
Artandi SE