| Autor: |
Tan, Lei, Duan, Xiaohua, Mutyala, Pratyusha, Zhou, Ting, Amin, Sadaf, Zhang, Tuo, Herbst, Brian, Askan, Gokce, Itkin, Tomer, Xiang, Zhaoying, Michelassi, Fabrizio, Lieberman, Michael D, Iacobuzio-Donahue, Christine A, Leach, Steven D, Evans, Todd, Chen, Shuibing |
| Zdroj: |
Journal of Molecular Cell Biology; Jun2023, Vol. 15 Issue 6, p1-15, 15p |
| Abstrakt: |
Chemoresistance is a primary cause of treatment failure in pancreatic cancer. Identifying cell surface markers specifically expressed in chemoresistant cancer cells (CCCs) could facilitate targeted therapies to overcome chemoresistance. We performed an antibody-based screen and found that TRA-1-60 and TRA-1-81, two 'stemness' cell surface markers, are highly enriched in CCCs. Furthermore, TRA-1-60+/TRA-1-81+ cells are chemoresistant compared to TRA-1-60–/TRA-1-81– cells. Transcriptome profiling identified UGT1A10 , shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and chemoresistance. From a high-content chemical screen, we identified Cymarin, which downregulates UGT1A10 , eliminates TRA-1-60/TRA-1-81 expression, and increases chemosensitivity both in vitro and in vivo. Finally, TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival, which highlights their potentiality for targeted therapy. Therefore, we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance, as well as a leading drug candidate to target this pathway. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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