Protein Kinase D2 controls pancreatic cancer cell invasion by secretion of trypsins PRSS1 and 3 as well as matrix-metalloproteases

The elucidation of signaling pathways regulating pancreatic cancer cell invasive properties is pivotal to control and develop strategies against metastasis. Protein Kinase D2 (PKD2) is strongly expressed in pancreatic cancer cells. We have recently identified PKD2 as a key regulator of trypsin (PRSS1, PRSS3) as well as matrix-metalloprotease (MMP) secretion in pancreatic cancer cells. PKD2 enhances PRSS1 and 3 expression as well as secretion. Both proteases are involved in cleavage of surface proteins such as the cell-cell adhesion protein E-Cadherin. Cleavage of E-Cadherin by trypsins generates fragments which…