Journal
NATURE CANCER
Volume 1, Issue 11, Pages 1082-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s43018-020-00125-0
Keywords
-
Categories
Funding
- National Institutes of Health (NIH)/NCI Cancer Center Support Grant [P30CA013696]
- NIH [R01 CA193442, R01 CA173481, R01 CA183929, P50 CA211024, U54CA209997, P50 CA097186, F31CA210607]
- DOD [W81XWH-17-1-0415]
- Stand Up To Cancer-Prostate Cancer Foundation Prostate Cancer Dream Team Award [SU2C-AACR-DT0712]
- Rutgers School of Health Professions
- Department of Defense Prostate Cancer Research Program [W81XWH-15-1-0185]
- Irving Institute/Clinical Trials Office Pilot Award - National Center for Advancing Translational Sciences, NIH [UL1TR001873]
- Irving Institute for Clinical and Translational Research at CUIMC [UL1TR001873]
- New Jersey Commission on Cancer Research Pre-Doctoral Fellowship [DCHS20PPC028]
- National Center for Advancing Translational Sciences, NIH [UL1TR001873]
- Prostate Cancer Foundation Young Investigator Award
- TJ Martell Foundation for Leukemia, Cancer and AIDS Research
- Prostate Cancer Foundation
Ask authors/readers for more resources
Understanding the intricacies of lethal prostate cancer poses specific challenges due to difficulties in accurate modeling of metastasis in vivo. Here we show that NPKEYFP 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. Using lineage tracing and molecular profiling, Abate-Shen and colleagues identify a Ras and Myc co-activation signature that predicts metastasis and castration resistance in localized prostate cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available