| Autor: |
Su Deng, Kathia E. Rodarte, Valli Annamalai, Ping Mu, Xiaoling Li, Carla Rodriguez Tirado, Jianfeng Ye, Lingfan Xu, Carlos Arana, Nickolas A. Johnson, Bo Li, U-Ging Lo, Jer-Tsong Hsieh, Julisa Gonzalez, Tao Wang, Lauren A. Metang, Zhiqun Xie, Donald J. Vander Griend, Yunguan Wang, Yaru Xu, Choushi Wang |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.11.02.466956 |
| Popis: |
Emerging evidence indicates that various cancers can gain resistance to targeted therapies by acquiring lineage plasticity. Although various genomic and transcriptomic aberrations correlate with lineage plasticity-driven resistance, the molecular mechanisms of acquiring lineage plasticity have not been fully elucidated. Through integrated transcriptomic and single cell RNA-Seq (scRNA-Seq) analysis of more than 80,000 cells, we reveal for the first time that the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling is a crucial executor in promoting lineage plasticity-driven AR targeted therapy resistance in prostate cancer. Ectopic activation of JAK-STAT signaling is specifically required for the AR targeted therapy resistance of subclones expressing multilineage, stem-like and epithelial-to-mesenchymal transition (EMT) lineage transcriptional programs and represents a potential therapeutic target for overcoming AR targeted therapy resistance.One-Sentence SummaryJAK-STAT signaling is a crucial executor in promoting lineage plasticity-driven AR therapy resistance in prostate cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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