An integrative proteomics approach to identify novel therapeutic targets for SPINK1-positive prostate cancer.

Dysregulated phosphorylation of proteins perturbs the activity of several biological pathways leading to tumorigenesis and metastases. Integrated proteomics studies offer an in-depth comprehension of cancer pathobiology, and could untangle its complex circuitries. To decipher the signaling involved in SPINK1-mediated tumorigenesis, we performed label-free quantitative proteome and phosphoproteome profiling of small hairpin RNA -mediated SPINK1 silenced (shSPINK1) and control small hairpin RNA Scrambled (shSCRM) 22RV1 cells. Our integrated proteomics data revealed ~4000 proteins and enriched ~6000 phosphopeptides in each biological replicate. Of these, 367 proteins and 807 phosphopeptides were found to be significantly altered between shSCRM and shSPINK1 cells.

蛋白质磷酸化失调会扰动多条生物通路的活性，进而引发肿瘤发生与转移。整合蛋白质组学研究能够深入解析癌症病理生物学机制，并厘清其复杂的信号调控网络。为解析SPINK1介导的肿瘤发生相关信号通路，本研究对短发夹RNA（small hairpin RNA, shRNA）介导的SPINK1沉默细胞（shSPINK1）及对照随机序列短发夹RNA（shSCRM）22RV1细胞开展了无标记定量蛋白质组与磷酸化蛋白质组谱分析。本研究的整合蛋白质组学数据显示，每个生物学重复样本中均可检测到约4000种蛋白质，并富集得到约6000个磷酸肽。其中，shSCRM与shSPINK1细胞间共有367种蛋白质及807个磷酸肽发生显著差异改变。