Parallel-Reaction-Monitoring-Based Proteome-Wide Profiling of Differential Kinase Protein Expression during Prostate Cancer Metastasis in Vitro

Prostate
cancer is the most common type of cancer in men, and kinases
are heavily pursued as drug targets for anticancer therapy. In this
study, we applied our recently reported parallel-reaction-monitoring
(PRM)-based targeted proteomic method to examine the reprogramming
of the human kinome associated with bone metastasis of prostate cancer
in vitro. The method displayed superior sensitivity over the shotgun-proteomic
approach, and it facilitated the quantification of the relative expression
of 276 kinase proteins in a pair of bone metastatic prostate cancer
cells. Among the differentially expressed kinases, mitogen-activated
protein kinase kinase kinase kinase 4 (MAP4K4) stimulates the migration
and invasion of cultured prostate cancer cells, partially by modulating
the activity of secreted matrix metalloproteinases 9 (MMP-9). We also
found that the upregulation of MAP4K4 in metastatic prostate cancer
cells is driven by the MYC proto-oncogene. Cumulatively,
we identify MAP4K4 as a potential promoter for prostate cancer metastasis
in vitro.