MassIVE MSV000096252

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An Integrated Proteomic Portrait of Prostate Cancer Progression

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Description

Cancer forms a local tumor that subsequently metastasizes to distant organs. In prostate cancer, the latter part of the trajectory is influenced by the inhibition of the androgen receptor (AR). The study of proteomic changes along disease progression may reveal insights into how prostate cancer evolves and open new therapeutic avenues. Here, we profile changes in protein abundance and post-translational modifications (PTMs) along the disease trajectory in patient-derived xenograft models. Our results suggest a key involvement of the RTK-RAS-MAPK pathway during disease progression. We highlight multiple alterations within this pathway including the tumor suppressors NF1 and ERF. Enhanced activity of cyclin-dependent kinases results in the engagement of various DNA repair pathways. Specific PTMs suggest changes in mitochondrial ATP synthesis, proteasomal activity, gene splicing, and TGF beta signaling. Finally, we show how different transcription factors engage with disease progression. A web resource is provided enabling the investigation of dynamic proteomic perturbations. [doi:10.25345/C5833N95G] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Prostate Cancer ; Disease Progression ; Resistance to Androgen Receptor Inhibition ; Lineage Plasticity ; Protein Phosphorylation, Ubiquitylation, and Acetylation ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Jean-Philippe Theurillat, Institute of Oncology Research, Bellinzona, Switzerland, Switzerland
Submitting User: Krivera23

Publications

Zhang J, Rivera KD, Bossi D, Gianfanti F, Nicastri S, Gomes D, Matkovic M, Coazzoli M, Mosole S, Costanzo F, Vallerga A, Ceserani V, Cavalli M, Virshup M, Burt RA, Bolis M, Ruthishauser D, Stathis A, Moch H, Bubendorf L, Cavalli A, Corey E, Wang Y, Mani DR, Carr SA, Udeshi N, Theurillat JP.
An integrated proteomic portrait of prostate cancer progression.
Cell Rep. 2025 Jun 24;44(6):115828. Epub 2025 Jun 13.

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