Protein Kinase D2 (PKD2) controls pancreatic cancer cell invasion and angiogenesis by secretion of trypsins PRSS1 and 3 as well as matrix-metalloproteases

The elucidation of signaling pathways controlling pancreatic cancer cell invasion and angiogenesis is pivotal to control and develop strategies against metastasis. Protein Kinase D2 (PKD2) is strongly expressed in pancreatic cancer cells. It is a key regulator of trypsin (PRSS1, PRSS3) as well as matrix-metalloprotease 7 and 9 (MMP 7 and 9) expression and secretion. PRSS1 and 3 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 interfere with cell-cell adhesion. Trypsins also act upstream of MMPs, e.g. by pr…