title: Proteomic Comparison and MRM-Based Comparative Analysis of Metabolites Reveal Metabolic Shift in Human Prostate Cancer Cell Lines.
abstract: One of the major challenges in prostate cancer therapy remains the development of effective treatments for castration-resistant prostate cancer (CRPC), as the underlying mechanisms for its progression remain elusive. Previous studies showed that androgen receptor (AR) is crucially involved in regulation of metabolism in prostate cancer (PCa) cells throughout the transition from early stage, androgen-sensitive PCa to androgen-independent CRPC. AR achieves such metabolic rewiring directively either via its transcriptional activity or via interactions with AMP-activated protein kinase (AMPK). However, due to the heterogeneous expression and activity status of AR in PCa cells, it remains a challenge to investigate the links between AR status and metabolic alterations. To this end, we compared the proteomes of three pairs of androgen-sensitive (AS) and androgen-independent (AI) PCa cell lines, namely, PC3-AR(+)/PC3, 22Rv1/Du145, and LNCaP/C42B, using an iTRAQ labeling approach. Our results revealed that most of the differentially expressed proteins between each pair function in metabolism, indicating a metabolic shift between AS and AI cells, as further validated by multiple reaction monitoring (MRM)-based quantification of nucleotides and relative comparison of fatty acids between these cell lines. Furthermore, increased adenylate kinase isoenzyme 1 (AK1) in AS relative to AI cells may result in activation of AMPK, representing a major regulatory factor involved in the observed metabolic shift in PCa cells.
authors.affiliation: ‡University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Shu
authors.forename: Tanxi
authors.initials: T
authors.lastname: Cai
authors.forename: Xiulan
authors.initials: X
authors.lastname: Chen
authors.affiliation: §State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Helen He
authors.initials: HH
authors.lastname: Zhu
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.forename: Nali
authors.initials: N
authors.lastname: Zhu
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Xie
authors.forename: Shasha
authors.initials: S
authors.lastname: Wei
authors.affiliation: ‡University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Niu
authors.affiliation: §State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
authors.forename: Fuquan
authors.initials: F
authors.lastname: Yang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods; D016000:Cluster Analysis; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009711:Nucleotides / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000145:classification / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D011944:Receptors, Androgen / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005227:Fatty Acids; D009711:Nucleotides; D010455:Peptides; D020543:Proteome; D011944:Receptors, Androgen; D000105:Acetyl Coenzyme A; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase; C110939:adenylate kinase 1
keywords: AMPK; CRPC; androgen receptor; metabolic shift; metabolite; quantitative proteomics