Journal
BIOMEDICINES
Volume 9, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines9101404
Keywords
castration resistant prostate cancer; proteome; metabolites; signaling pathway; androgen
Categories
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2015R1C1A1A02036315, 2018R1A2B6001241]
- National Cancer Center [NCC-2110521]
- National Research Foundation of Korea [2018R1A2B6001241, 2015R1C1A1A02036315] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This study identified eight proteins with significant changes in expression in response to androgen-induced and androgen-bypassing signaling, revealing their involvement in metabolic processes and cancer. The findings also indicated increased expression levels of these proteins in prostate cancer patients, providing insights into possible molecular mechanisms of castration-resistant prostate cancer (CRPC).
Androgen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, especially that of androgen, continues to be an important strategy for treating prostate cancer patients, the disease ultimately progresses to castration-resistant prostate cancer (CRPC), despite a continuous hormone-deprived environment. To date, it remains unclear which pathways in this progression are active and targetable. Here, we performed a proteomic analysis of VCaP cells stimulated with androgen or forskolin to identify proteins specific for androgen-induced and androgen-bypassing signaling, respectively. Patterns of differentially expressed proteins were quantified, and eight proteins showing significant changes in expression were identified. Functional information, including a Gene Ontology analysis, revealed that most of these proteins are involved in metabolic processes and are associated with cancer. The mRNA and protein expression of selected proteins was validated, and functional correlations of identified proteins with signaling in VCaP cells were assessed by measuring metabolites related to each enzyme. These analyses offered new clues regarding effector molecules involved in prostate cancer development, insights that are supported by the demonstration of increased expression levels of the eight identified proteins in prostate cancer patients and assessments of the progression-free interval. Taken together, our findings show that aberrant levels of eight proteins reflect molecular changes that are significantly regulated by androgen and/or PKA signaling pathways, suggesting possible molecular mechanisms of CRPC.
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