Cancer metastasis is the cause of most cancer related deaths and many cancers are becoming resistant to current therapies. An alternative approach is to investigating signalling pathways that cause cancer cell migration such as chemokine signalling pathways. Such downstream signalling proteins are PKC and PKD. Therefore, we investigated the role of these two proteins in CXCL12 mediated PC3 prostate cancer migration. Whereas PKC and PKD inhibitors do not affect the release of calcium in PC3 prostate cancer cells, both are involved in migration, particularly inhibition of the atypical PKC isoform PKC zeta causes the greatest reduction in PC3 cell migration. Classical and/or Novel PKC isoform inhibition changes the shape of the PC3 cells, they show a more rounded morphology, whereas PKD inhibition causes prostate cancer cell to elongate. PKC zeta inhibition causes the enlargement of PC3 area possibly due to dysregulated actin cytoskeletal control. These results highlight the importance of verifying which signalling proteins, in which cell and in which chemokine signalling cascade enable cancer cellular migration. Crown Copyright (C) 2019 Published by Elsevier Inc. All rights reserved.