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| Status |
Public on Jul 18, 2019 |
| Title |
The Polycomb Repressor Complex 1 Drives Double-Negative Prostate Cancer Metastasis by Coordinating Stemness and Immune Suppression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The mechanisms that enable immune evasion at metastatic sites are poorly understood. We show that the Polycomb Repressor Complex 1 (PRC1) drives colonization of the bones and visceral organs in double-negative prostate cancer (DNPC). In vivo genetic screening identifies CCL2 as the top prometastatic gene induced by PRC1. CCL2 governs self-renewal and induces the recruitment of M2-like tumor-associated macrophages and regulatory T cells, thus coordinating metastasis initiation with immune suppression and neoangiogenesis. A catalytic inhibitor of PRC1 cooperates with immune checkpoint therapy to reverse these processes and suppress metastasis in genetically engineered mouse transplantation models of DNPC. These results reveal that PRC1 coordinates stemness with immune evasion and neoangiogenesis and point to the potential clinical utility of targeting PRC1 in DNPC.
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| |
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| Overall design |
PC3 prostate cancer cells stably expressing RNF2 shRNA or Scramble shRNA, or treated with PRT4165 or GW-516.
|
| Web link |
https://www.sciencedirect.com/science/article/pii/S1535610819303009?via%3Dihub
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| |
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| Contributor(s) |
Su W, Han H, Wang Y, Zhang B, Zhou B, Cheng Y, Rumandla A, Chakraborty G, Su J, Yang G, Wang G, Rosen N, Scher HI, Ouerfelli O, Giancotti FG |
| Citation(s) |
31327655 |
| |
| Submission date |
Aug 24, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Wenjing Su |
| E-mail(s) |
wjsu06@gmail.com
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Street address |
1275 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (10)
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| Relations |
| BioProject |
PRJNA400081 |
| SRA |
SRP116142 |
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