RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance
Harvard University · Massachusetts General Hospital · +2 more institutions
Abstract
Prostate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging; hence, sampling circulating tumor cells (CTCs) may reveal drug-resistance mechanisms. We established single-cell RNA-sequencing (RNA-Seq) profiles of 77 intact CTCs isolated from 13 patients (mean six CTCs per patient), by using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing under treatment with an AR inhibitor, compared with untreated cases,…
Citation impact
- FWCI
- 64.93
- Percentile
- 100%
- References
- 37
Authors
23- DTDavid T. MiyamotoCorresponding
Harvard University, Massachusetts General Hospital, Center for Cancer Research
- YZYu ZhengCorresponding
Howard Hughes Medical Institute, Massachusetts General Hospital, Center for Cancer Research
- BSBen S. Wittner
Harvard University, Massachusetts General Hospital, Center for Cancer Research
- RJRichard J. Lee
Harvard University, Massachusetts General Hospital, Center for Cancer Research
- HZHuili Zhu
Massachusetts General Hospital, Center for Cancer Research
Topics & keywords
- Wnt signaling pathway
- Antiandrogen
- Prostate cancer
- Prostate
- RNA
- Cancer research
- Resistance (ecology)
- Biology
- Good health and well-being
Funding
- UDU.S. Department of Defense
- HHHoward Hughes Medical Institute
- BWBurroughs Wellcome Fund
- PCProstate Cancer Foundation
- MGMassachusetts General Hospital
- NINational Institutes of HealthAward: EB008047
- JAJohnson and Johnson
- SUStand Up To Cancer
- NCNational Cancer InstituteAward: 2RO1CA129933
- NINational Institute of Biomedical Imaging and Bioengineering