A targetable pathway to eliminate TRA-1-60(+) /TRA-1-81(+) chemoresistant cancer cells Journal Article
| Authors: | Tan, L.; Duan, X.; Mutyala, P.; Zhou, T.; Amin, S.; Zhang, T.; Herbst, B.; Askan, G.; Itkin, T.; Xiang, Z.; Michelassi, F.; Lieberman, M. D.; Iacobuzio-Donahue, C. A.; Leach, S. D.; Evans, T.; Chen, S. |
| Editor: | Lu, H. |
| Article Title: | A targetable pathway to eliminate TRA-1-60(+) /TRA-1-81(+) chemoresistant cancer cells |
| Abstract: | 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. Further- more, 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. © The Author(s) (2023). |
| Keywords: | pancreatic neoplasms; gene expression profiling; drug resistance; drug resistance, neoplasm; cell line, tumor; pancreas tumor; tumor cell line; pancreatic cancer; chemoresistance; cymarin; humans; human; tra-1-60/tra-1-81; ugt1a10 |
| Journal Title: | Journal of Molecular Cell Biology |
| Volume: | 15 |
| Issue: | 6 |
| ISSN: | 1674-2788 |
| Publisher: | Oxford University Press |
| Date Published: | 2023-06-01 |
| Start Page: | mjad039 |
| Language: | English |
| DOI: | 10.1093/jmcb/mjad039 |
| PUBMED: | 37327088 |
| PROVIDER: | scopus |
| PMCID: | PMC10847630 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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