核糖体生物发生
甲状腺癌
癌症研究
生物
转录组
甲状腺乳突癌
癌症
甲状腺
核糖体RNA
甲状腺癌
肿瘤进展
核糖体
分子生物学
核糖核酸
基因
基因表达
遗传学
作者
Pil Mun Yu,Nannan Qu,Rui Zhu,Jia‐Qian Hu,Hao Peng,Jiale Wu,Licheng Tan,Hualei Gan,Cong He,Chuantao Fang,Yubin Lei,Jian Li,Chenxi He,Fei Lan,Xiao Shi,Wenjun Wei,Yu Wang,Qinghai Ji,Fa-Xing Yu,Yulong Wang
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-09-01
卷期号:9 (35)
被引量:6
标识
DOI:10.1126/sciadv.adg7125
摘要
TERT reactivation occurs frequently in human malignancies, especially advanced cancers. However, in vivo functions of TERT reactivation in cancer progression and the underlying mechanism are not fully understood. In this study, we expressed TERT and/or active BRAF ( BRAF V600E) specifically in mouse thyroid epithelium. While BRAF V600E alone induced papillary thyroid cancer (PTC), coexpression of BRAF V600E and TERT resulted in poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome analysis revealed that tumors from mice coexpressing BRAF V600E and TERT were highly heterogeneous, and cell dedifferentiation was positively correlated with ribosomal biogenesis. Mechanistically, TERT boosted ribosomal RNA (rRNA) expression and protein synthesis by interacting with multiple proteins involved in ribosomal biogenesis. Furthermore, we found that CX-5461, an rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation of thyroid cancer. Thus, TERT promotes thyroid cancer progression by inducing cancer cell dedifferentiation, and ribosome inhibition represents a potential strategy to treat TERT-reactivated cancers.
科研通智能强力驱动
Strongly Powered by AbleSci AI