| Accession |
PRJCA016635 |
| Title |
TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
Raw sequence reads
|
| Organisms |
Mus musculus
|
| Description |
TERT reactivation occurs frequently in human malignancies. While BRAF activating mutation widely existed in cancers at various stages, TERT react ivation mainly occurs in advanced tumors. However, in vivo evidence for TERT role in cancer progression and the underlying mechanism is currently lacking. In this study, we induced TERT and/or BRAF V600E expression in mouse thyroid epithelium. TERT overexpression alone had no evident effect on tumor initiation. BRAFVE expression itself induced mediocre papillary thyroid cancer (PTC). Notably, the co-expression of BRAFVE and TERT resulted in aggressive poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome revealed that tumors from co-mutant mice were highly heterogeneous and dedifferentiation process significantly correlated with ribosomal pathways. Mechanistically, TERT boosted ribosomal RNA expression and protein synthesis. CX-5461, a rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation. Thus, TERT promotes thyroid cancer progression by inducing dedifferentiation, and ribosome biogenesis inhibition represents a potential treatment strategy for TERT-reactivated cancers. |
| Sample scope |
Multiisolate |
| Release date |
2023-12-31 |
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
|
81972501
|
|
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
National Key Technologies R&D Program
|
2018YFA0800304
|
|
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
National Key Technologies R&D Program
|
2020YFA0803202
|
|
| Science and Technology Commission of Shanghai Municipality
|
|
21S11905000
|
|
| Shanghai Shenkang Hospital Development Center
|
|
SHDC22021201
|
|
|
|
| Submitter |
Yulong
Wang (headneck@126.com)
|
| Organization |
Fudan University Shanghai Cancer Center |
| Submission date |
2023-04-27 |
