Salivary adenoid cystic carcinoma (SACC) is a malignant tumor, which is characterized by a higher incidence of distant metastasis. The aim of this study was to investigate the role and mechanism of protein kinase D1 (PKD1) in regulating the epithelial-mesenchymal transition (EMT) and promotes the metastasis in SACC. We analyzed the expression of PKD1 in 40 SACC patients and different metastatic potential cell lines. Then, we investigated whether the migration and growth of SACC were regulated by PKD1 using shRNA interference or inhibition of kinase active in vitro cell. Moreover, the mechanism by which PKD1 regulates the stability of Snail protein was determined. Finally, nude mice were used to testify the function of PKD1 via tail vein injection. PKD1 was correlated with metastasis and poor prognosis of SACC patients. PKD1 inhibition attenuated proliferation, migration, invasion, and EMT of SACC cells. Conversely, kinase active PKD1 could induce EMT and promoted cell migration in human HSG cell. Furthermore, downregulation of PKD1 regulated Snail via phosphorylation at Ser-11 on Snail protein and promotion of proteasome-mediated degradation, and reduced lung metastasis in vivo. Our results suggest that PKD1 induces the EMT and promotes the metastasis, which illustrate that PKD1 may be a potential prognostic biomarker and serve as a potential therapeutic target for SACC patients.

Protein kinase D1 induced epithelial-mesenchymal transition and invasion in salivary adenoid cystic carcinoma via E-cadherin/Snail regulation.

Recent scientific research demonstrates that protein kinases of PKD family affect biological features of normal and malignant cells. Differential expression of PKD genes was found in tumors of different histogenesis. These protein kinases could be activated by growth factors, antigen stimulation, and oxidative stress, the processes that usually can be observed during tumor progression. PKD regulate cell-cell contacts by affecting cell adhesion. PKD are involved in the regulation of cell proliferation and apoptosis, and also participate in epigenetic regulation of gene expression. That is why studies of differential expression and activity of PKD1, PKD2 and PKD3 in the context of tumor spreading and prognosis could be the perspective subject of translational research in oncology. This will contribute to the development of new approaches to differential diagnostics of tumor and target therapy, and also reveal prognostic factors for the prediction of clinical outcome.

Mikhalap Sv

Papers

Protein kinases of PKD family as a potential object of translational research in oncology