Proteomic Landscape of Prostate Cancer: The View Provided by Quantitative Proteomics, Integrative Analyses, and Protein Interactomes

SIMPLE SUMMARY: Recent methodological developments have enabled studying proteins on a large scale in a quantitative fashion, which helps in building comprehensive views of specific molecular settings. These proteomics approaches, and combining their information to genomics and transcriptomics, have revealed that not all genetic and transcriptomic aberrations in prostate cancer are translated to the proteome. This makes it important to understand which ones are translated. Here, we review recent large-scale proteomics studies on clinical prostate cancer and prostate cancer models which help us understand how prostate cancer develops and evades current drug treatments. ABSTRACT: Prostate cancer is the second most frequent cancer of men worldwide. While the genetic landscapes and heterogeneity of prostate cancer are relatively well-known already, methodological developments now allow for studying basic and dynamic proteomes on a large scale and in a quantitative fashion. This aids in revealing the functional output of cancer genomes. It has become evident that not all aberrations at the genetic and transcriptional level are translated to the proteome. In addition, the proteomic level contains heterogeneity, which increases as the cancer progresses from primary prostate cancer (PCa) to metastatic and castration-resistant prostate cancer (CRPC). While multiple aspects of prostate adenocarcinoma proteomes have been studied, less is known about proteomes of neuroendocrine prostate cancer (NEPC). In this review, we summarize recent developments in prostate cancer proteomics, concentrating on the proteomic landscapes of clinical prostate cancer, cell line and mouse model proteomes interrogating prostate cancer-relevant signaling and alterations, and key prostate cancer regulator interactomes, such as those of the androgen receptor (AR). Compared to genomic and transcriptomic analyses, the view provided by proteomics brings forward changes in prostate cancer metabolism, post-transcriptional RNA regulation, and post-translational protein regulatory pathways, requiring the full attention of studies in the future.