Proto-Oncogene Serine/Threonine Kinase PIM3 Promotes Cell Migration via Modulating Rho GTPase Signaling

The
proto-oncogene serine/threonine-protein kinase PIM3 plays critical
roles in cancer, and it has been extensively exploited as a drug target.
Here, we investigated the quantitative changes in the cellular proteome
and phosphoproteome in liver cancer cells overexpressing PIM3 to obtain
a better understanding of the regulatory functions of PIM3 and the
underlying molecular mechanisms. This work depicted the landscape
of gene expression and protein phosphorylation potentially regulated
by PIM3. A signaling network analysis showed that PIM3 may coordinate
various cellular processes, for example, signal transduction, cell
cycle, apoptosis, and so forth. Intriguingly, quantitative phosphoproteomics
revealed that the PIM3 overexpression elevated the phosphorylation
of multiple Rho GTPase modulators that target RhoA, a central modulator
of cell movement. Further investigations confirmed that PIM3 activated
RhoA to subsequently regulate cytoskeletal rearrangements and cell
migration. Taken together, this study comprehensively mapped the proteome
and phosphoproteome regulated by PIM3 and revealed its role in promoting
liver cancer cell migration and invasion by modulating Rho GTPase
signaling.