Identification of the Septin complex: a novel co-activator of the Androgen Receptor

BIZZOTTO, JUAN ANTONIO; SANCHIS, PABLO ANTONIO; NEMIROVSKI, SERGIO; GUERON, GERALDINE; VALACCO, PIA; SCORTICATTI, CARLOS; VAZQUEZ, ELBA SUSANA; LAGE VICKERS, SOFÍA; MAZZA, OSVALDO; COTIGNOLA, JAVIER; BIZZOTTO, JUAN ANTONIO; SANCHIS, PABLO ANTONIO; NEMIROVSKI, SERGIO; GUERON, GERALDINE; VALACCO, PIA; SCORTICATTI, CARLOS; VAZQUEZ, ELBA SUSANA; LAGE VICKERS, SOFÍA; MAZZA, OSVALDO; COTIGNOLA, JAVIER

Congreso; Advances in prostate cancer research; 2020

Deciphering how proteins interact is critical to understand cellular processes. Although it is well knownthat prostate cancer (PCa) is a progressive disease involving multiple gene alterations, little is known atthe proteome level. Most of the functional information of the cancer-associated genes relies in theproteome, an exceptionally complex biological system involving several proteins that function throughdynamic protein-protein interactions and post-translational modifications. To identify and assess PCaproteomes, we carried out an in-depth proteomics analysis using human PCa and Benign ProstaticHyperplasia (BPH) formalin-fixed, paraffin-embedded (FFPE) tissue samples and explored proteincomplexes within samples.We combined a new protein extraction procedure that disrupts the crosslinked proteins from the FFPEtissue samples and then screened proteins by ESI-MS/MS. We found 109 proteins enriched in PCacompared with BPH samples.Among the available interactome mapping methods, we took a departure from conventional proteomicsanalysis approaches, and focused on biological networks. We used CORUM, a database of human proteincomplexes formed by curated physically interacting proteins, to identify protein complexes (PCs)differentially expressed in PCa and BPH tissues. These PCs can be regarded as units of biologicalfunction, hence suitable for contextualizing proteomics data. In this regard, using PCs as a cluster vector,we calculated a Proteomics Signature Profile (PSP) for each sample based on the hit rates of theirreported proteins against the cluster vector.Our results show 5 differentially expressed protein complexes in PCa compared with BPH (P