Bibliographic Details
| Title: |
Overexpression of TBX3 suppresses tumorigenesis in experimental and human cholangiocarcinoma |
| Authors: |
Shanshan Deng, Xinjun Lu, Xue Wang, Binyong Liang, Hongwei Xu, Doris Yang, Guofei Cui, Andrew Yonemura, Honor Paine, Yi Zhou, Yi Zhang, Maria Maddalena Simile, Francesco Urigo, Matthias Evert, Diego F. Calvisi, Benjamin L. Green, Xin Chen |
| Source: |
Cell Death and Disease, Vol 15, Iss 6, Pp 1-11 (2024) |
| Publisher Information: |
Nature Publishing Group, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
Abstract TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-024-06839-8 |
| Access URL: |
https://doaj.org/article/904e8d75b78a4941a72af5c5e04ec7b8 |
| Accession Number: |
edsdoj.904e8d75b78a4941a72af5c5e04ec7b8 |
| Database: |
Directory of Open Access Journals |
