Targeted Quantitative Kinome Analysis Identifies PRPS2 as a Promoter for Colorectal Cancer Metastasis

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.