| Literature DB >> 34085047 |
Juan M Arriaga1, Sukanya Panja2, Mohammed Alshalalfa3, Junfei Zhao4,5, Min Zou1,6, Arianna Giacobbe1, Chioma J Madubata4,5,7, Jaime Yeji Kim1, Antonio Rodriguez8,9, Ilsa Coleman10, Renu K Virk11, Hanina Hibshoosh11,12, Onur Ertunc13,14,15,16,17, Büşra Ozbek13,14,15,16, Julia Fountain15, R Jeffrey Karnes18, Jun Luo15,16, Emmanuel S Antonarakis14,15,16, Peter S Nelson10, Felix Y Feng3,19,20,21, Mark A Rubin8, Angelo M De Marzo13,14,15,16, Raul Rabadan4,5,12, Peter A Sims4,12,22, Antonina Mitrofanova23, Cory Abate-Shen24,25,26,27,28.
Abstract
Understanding the intricacies of lethal prostate cancer poses specific challenges due to difficulties in accurate modeling of metastasis in vivo. Here we show that NPK EYFP mice (for Nkx3.1 CreERT2/+ ; Pten flox/flox ; Kras LSL-G12D/+ ; R26R-CAG-LSL-EYFP/+) develop prostate cancer with a high penetrance of metastasis to bone, thereby enabling detection and tracking of bone metastasis in vivo and ex vivo. Transcriptomic and whole-exome analyses of bone metastasis from these mice revealed distinct molecular profiles conserved between human and mouse and specific patterns of subclonal branching from the primary tumor. Integrating bulk and single-cell transcriptomic data from mouse and human datasets with functional studies in vivo unravels a unique MYC/RAS co-activation signature associated with prostate cancer metastasis. Finally, we identify a gene signature with prognostic value for time to metastasis and predictive of treatment response in human patients undergoing androgen receptor therapy across clinical cohorts, thus uncovering conserved mechanisms of metastasis with potential translational significance.Entities:
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Year: 2020 PMID： 34085047 PMCID： PMC8171279 DOI： 10.1038/s43018-020-00125-0
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347