Polo family kinase 4 (Plk4) is required for mitotic progression, and is haploinsufficient for tumor suppression and timely hepatocyte polarization in regenerating liver. At the same time, recent evidence suggests that Plk4 expression may have a role in clinical cancer progression, although the mechanisms are not clear. Here we identify a gene expression pattern predictive of reduced motility in Plk4(+/-) murine embryonic fibroblasts (MEFs) and validate this prediction with functional assays of cell spreading, migration and invasion. Increased Plk4 expression enhances cell spreading in Plk4(+/-) MEFs and migration in human embryonic kidney 293T cells, and increases invasion by DLD-1 colon cancer cells. Plk4 depletion impairs invasion of wild-type MEFs and suppresses invasion by MDA-MB231 breast cancer cells. Cytoskeletal reorganization and development of polarity are impaired in Plk4-deficient cells that have been stimulated to migrate. Endogenous Plk4 phosphorylated at the autophosphorylation site S305 localizes to the protrusions of motile cells, coincident with the RhoA GEF Ect2, GTP-bound RhoA and the RhoA effector mDia. Taken together, our findings reveal an unexpected activity of Plk4 that promotes cell migration and may underlie an association between increased Plk4 expression, cancer progression and death from metastasis in solid tumor patients.

Reconstruction by PG decreases the rate of PF in comparison with PJ. Surgeons should consider reconstructing the pancreatic remnant following PD with PG, particularly in patients at high risk for PF.

Recent major advancements in the technique and intraoperative management have significantly improved outcomes of hepatic surgery (1). However, post-operative liver failure remains a significant complication, responsible for 60% to 100% of deaths after liver resection (1-4).Considering the rising prevalence of parenchymal liver disease and the increased use of potentially hepatotoxic neoadjuvant chemotherapy, more patients are and will be at risk of post-hepatectomy liver failure (PHLF) (5,6).While initial liver insufficiency (ILI), whereby serum bilirubin and international normalized ratio (INR) rise in the first 24 to 72 hours following hepatectomy, is frequent, it is most often transient (7) 65.0%; P=0.03). Conclusions:In patients who experience post-hepatectomy ILI, HP is associated with improved recovery, potentially indicating more efficient liver regeneration. Further studies should explore the usefulness of posthepatectomy HP as an early prognostic factor of recovery from ILI.