Identification of druggable targets from the interactome of the Androgen Receptor and Serum Response Factor pathways in prostate cancer.

Background: The Androgen Receptor (AR) is crucial for prostate cancer (PCa) progression. Despite the introduction of second-generation AR antagonist, majority of patients develop resistance. The Serum Response Factor (SRF) was identified as a player involved in a crosstalk with AR signalling pathway and associated resistance. Elevated SRF levels in PCa patients were associated with disease progression and resistance to enzalutamide. However, the molecular mediators of the crosstalk between SRF and AR still need to be elucidated. The objective of this study was to identify common interactors of the AR/SRF crosstalk as therapeutic targets. Methods: Here we used affinity purification mass spectrometry (MS) to identify proteins that interact with both SRF and AR. Results: Seven common interactors were identified, including HSP70, HSP0AA1, HSP90AB1, HSAP5, PRDX1 and GAPDH. Pathway analysis revealed that the PI3k/AKT pathway was the most enriched in the AR/SRF network. Moreover, pharmacological inhibition of several proteins in this network, including HSP70, HSP90, PI3k and AKT, significantly decreased cellular viability of PCa cells. Conclusions: This study identified a list of AR/SRF common interactors that represent a pipeline of druggable targets for the treatment of PCa.