The Polycomb Repressor Complex 1 drives double-negative prostate cancer metastasis by coordinating stemness and immune suppression Journal Article

   

Authors:	Su, W.; Han, H. H.; Wang, Y.; Zhang, B.; Zhou, B.; Cheng, Y.; Rumandla, A.; Gurrapu, S.; Chakraborty, G.; Su, J.; Yang, G.; Liang, X.; Wang, G.; Rosen, N.; Scher, H. I.; Ouerfelli, O.; Giancotti, F. G.
Article Title:	The Polycomb Repressor Complex 1 drives double-negative prostate cancer metastasis by coordinating stemness and immune suppression
Abstract:	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. Copyright © 2019 Elsevier Inc. All rights reserved.
Keywords:	metastasis; angiogenesis; epigenetics; combination therapy; immune evasion; stemness; immune microenvironment; mdscs; tregs; preclinical compound
Journal Title:	Cancer Cell
Volume:	36
Issue:	2
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2019-08-12
Start Page:	139
End Page:	155.e10
Language:	English
DOI:	10.1016/j.ccell.2019.06.009
PUBMED:	31327655
PROVIDER:	scopus
PMCID:	PMC7210785
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070184267&doi=10.1016%2fj.ccell.2019.06.009&partnerID=40&md5=f277558989351a6425125d6e801a557a
Notes:	Article -- Source: Scopus

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