Suppression of cell migration by protein kinase Cδ

The ability of cancer cells to migrate is strongly correlated with malignant progression and metastasis. Survival signals that suppress apoptosis have also been linked to increased cell motility. We previously reported that suppression of protein kinase Cδ (PKCδ) provided survival signals in a rat fibroblast model system. These studies have been extended to human breast cancer cells with differential cell motilities and PKCδ levels. BT-549 cells, which lack detectable expression of PKCδ, migrate very efficiently, whereas MCF-7 cells, which express high levels of PKCδ, migrate very poorly. Ectopic expression of PKCδ suppressed cell migration in the BT-549 cells, and downregulation of PKCδ enhanced cell migration in the MCF-7 cells. Downregulation of PKCδ in the MCF-7 cells also led to increased secretion of the matrix metalloprotease MMP-9. The migration of mouse embryo fibroblasts (MEFs) from wild type and PKCδ knockout mice was also examined and MEFs from PKCδ knockout mice had a five-fold increase in eel migration relative to the wild-type MEFs. These data provide evidence that PKCδ suppresses cell migration in both human breast cancer cells and in primary mouse fibroblasts, and indicate that the loss of PKCδ in human cancers could contribute to both eel survival and metastasis.