Suppression of cell migration by protein kinase Cδ

Desmond Jackson, Yang Zheng, Donggon Lyo, Yinjie Shen, Keiko Nakayama, Keiichi I. Nakayama, Michael J. Humphries, Mary E. Reyland, David A. Foster

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3067-3072
Number of pages6
JournalOncogene
Volume24
Issue number18
DOIs
Publication statusPublished - 2005 Apr 21
Externally publishedYes

Keywords

  • Breast cancer cells
  • Cell migration
  • Metastasis
  • Protein kinase Cδ

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Jackson, D., Zheng, Y., Lyo, D., Shen, Y., Nakayama, K., Nakayama, K. I., Humphries, M. J., Reyland, M. E., & Foster, D. A. (2005). Suppression of cell migration by protein kinase Cδ. Oncogene, 24(18), 3067-3072. https://doi.org/10.1038/sj.onc.1208465