| Autor: |
Su Deng, Choushi Wang, Yunguan Wang, Yaru Xu, Xiaoling Li, Nickolas A. Johnson, Atreyi Mukherji, U-Ging Lo, Lingfan Xu, Julisa Gonzalez, Lauren A. Metang, Jianfeng Ye, Carla Rodriguez Tirado, Kathia Rodarte, Yinglu Zhou, Zhiqun Xie, Carlos Arana, Valli Annamalai, Xihui Liu, Donald J. Vander Griend, Douglas Strand, Jer-Tsong Hsieh, Bo Li, Ganesh Raj, Tao Wang, Ping Mu |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Nature Cancer. 3:1071-1087 |
| ISSN: |
2662-1347 |
| DOI: |
10.1038/s43018-022-00431-9 |
| 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, the molecular mechanisms enabling the acquisition of lineage plasticity have not been fully elucidated. We reveal that Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling is a crucial executor in promoting lineage plasticity-driven androgen receptor (AR)-targeted therapy resistance in prostate cancer. Importantly, ectopic JAK–STAT activation is specifically required for the resistance of stem-like subclones expressing multilineage transcriptional programs but not subclones exclusively expressing the neuroendocrine-like lineage program. Both genetic and pharmaceutical inhibition of JAK–STAT signaling resensitizes resistant tumors to AR-targeted therapy. Together, these results suggest that JAK–STAT are compelling therapeutic targets for overcoming lineage plasticity-driven AR-targeted therapy resistance. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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