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Cited by 17Prostate Cancer Treatment and ResearchAdvanced Proteomics Techniques and ApplicationsUbiquitin and proteasome pathways

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Single-Cell Proteomic Characterization of Drug-Resistant Prostate Cancer Cells Reveals Molecular Signatures Associated with Morphological Changes

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Woo, Jongmin, Loycano, Michael, Amanullah, Md, Qian, Jiang, Amend, Sarah R., Pienta, Kenneth J., Zhang, Hui·2025·Molecular & Cellular Proteomics
DOI 10.1016/j.mcpro.2025.100949PMC PMC12008537

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Abstract

This study delves into the proteomic intricacies of drug-resistant cells (DRCs) within prostate cancer, which are known for their pivotal roles in therapeutic resistance, relapse, and metastasis. Utilizing single-cell proteomics (SCP) with an optimized high-throughput data-independent acquisition (DIA) approach with the throughput of 60 sample per day, we characterized the proteomic landscape of DRCs in comparison to parental PC3 cells. This DIA method allowed for robust and reproducible protein quantification at the single-cell level, enabling the identification and quantification of over 1300 proteins per cell on average. Distinct proteomic sub-clusters within the DRC population were identified, closely linked to variations in cell size. The study uncovered novel protein signatures, including the regulation of proteins critical for cell adhesion and metabolic processes, as well as the upregulation of surface proteins and transcription factors pivotal for cancer progression. Furthermore, by conducting single-cell RNA-seq (scRNA-seq) analysis, we identified six upregulated and 10 downregulated genes consistently altered in drug-treated cells across both SCP and scRNA-seq platforms. These findings underscore the heterogeneity of DRCs and their unique molecular signatures, providing valuable insights into their biological behavior and potential therapeutic targets.

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Metadata

Authors
Woo, J., Loycano, M., Amanullah, M., Qian, J., Amend, S. R., Pienta, K. J., & Zhang, H.
Affiliations
Johns Hopkins University (US)
Corresponding author
Zhang, Hui
ORCID
Venue
Molecular & Cellular Proteomics
Publisher
Elsevier BV
Published
2025-04
Volume
24
Issue
4
Pages
100949
ISSN
1535-9476 (ISSN-L)
DOI
10.1016/j.mcpro.2025.100949
PMC
PMC12008537
OpenAlex
W4408432679
Cited by
17
References
2
Citations by year
2026: 11 · 2025: 6
FWCI
11.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular & Cellular Proteomics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institutes of Health National Cancer Institute (CA093900)
  • DOD Prostate Cancer Research Program (W81XWH-20-10353, W81XWH-22-1-0680)
  • U.S. Department of Defense
  • Patrick C. Walsh Prostate Cancer Research Fund
  • Congressionally Directed Medical Research Programs
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
single-cell proteomics, data-independent acquisition, proteomic heterogeneity, cell size variation, cell adhesion proteins, cancer metabolism, surface proteins, transcription factors, drug resistance, PC-3 cells, single-cell RNA sequencing, therapeutic target

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