Targeted Quantitative Kinome Analysis Identifies PRPS2 as a Promoter for Colorectal Cancer Metastasis
Targeted Quantitative Kinome Analysis Identifies PRPS2 as a Promoter for Colorectal Cancer Metastasis
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DOI：
10.1021/acs.jproteome.9b00119
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发表时间：
2019-05-01
影响因子：
4.4
通讯作者：
Wang, Yinsheng
中科院分区：
文献类型：
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作者：
Miao, Weili;Wang, Yinsheng
激酶是参与细胞信号传导的最重要的酶家族之一。在这项研究中，我们采用了最近开发的基于平行反应监测（PRM）的靶向蛋白质组学方法来研究结直肠癌（CRC）转移过程中人类激酶组的重编程。我们能够定量一对匹配的原发性/转移性CRC细胞系中299种激酶蛋白的相对表达。我们还发现，在差异表达的激酶中，磷酸核糖焦磷酸合成酶2（PRPS 2）通过调节基质金属蛋白酶9（MMP-9）的活性和E-cadherin的表达促进培养的CRC细胞的迁移和侵袭。此外，我们发现PRPS 2在转移性CRC细胞中的上调可以由MYC原癌基因诱导。总之，我们的无偏见的激酶组分析方法导致PRPS 2首次被鉴定为CRC转移的启动子。
Kinases are among the most important families of enzymes involved in cell signaling. In this study, we employed a recently developed parallel-reaction monitoring (PRM)-based targeted proteomic method to examine the reprogramming of the human kinome during colorectal cancer (CRC) metastasis. We were able to quantify the relative expression of 299 kinase proteins in a pair of matched primary/metastatic CRC cell lines. We also found that, among the differentially expressed kinases, phosphoribosyl pyrophosphate synthetase 2 (PRPS2) promotes the migration and invasion of cultured CRC cells through regulating the activity of matrix metalloproteinase 9 (MMP-9) and the expression of E-cadherin. Moreover, we found that the up-regulation of PRPS2 in metastatic CRC cells could be induced by the MYC proto-oncogene. Together, our unbiased kinome profiling approach led to the identification, for the first time, of PRPS2 as a promoter for CRC metastasis.