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PKC inhibition increases gap junction intercellular communication and cell adhesion in human neuroblastoma

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Abstract

Gap junction intercellular communication and cell–cell adhesion are essential for maintaining a normal cellular phenotype, including the control of growth and proliferation. Loss of either cell–cell adhesion or communication is common in cancers, while restoration of function is associated with tumor suppression. Protein kinase C (PKC) isozymes regulate a broad spectrum of cellular functions including growth and proliferation, and their overexpression has been correlated with carcinogenesis. Consequently, PKC inhibitors are currently undergoing clinical trials as an anti-cancer agents although the precise cellular alterations induced by PKC inhibitors remain to be elucidated. In the current study, the effects of PKC inhibitors on cell interactions were investigated using human neuroblastoma (IMR32, SKNMC, and SHSY-5Y) cell lines. An analysis of intercellular communication revealed an increase in gap junctional coupling with PKC inhibition. The observed increase in coupling was not associated with a change in Connexin43 distribution or an alteration of phosphorylation status of the protein. There was also an increase in cell–cell adhesion with PKC inhibitor treatment as indicated by a cell aggregation assay. Therefore, the growth suppressive abilities of PKC inhibition on tumors may be due to the cancer suppressive effects of increased gap junction intercellular communication and cell–cell adhesion.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, N6A 5C1, Canada

    Melissa Morley, Claire Jones, Mandeep Sidhu, Vishal Gupta, Suzanne M. Bernier, Walter J. Rushlow & Daniel J. Belliveau

  2. Department of Psychiatry, London Health Sciences Centre–University Campus, London, ON, N6A 5C1, Canada

    Walter J. Rushlow

  3. School of Health Studies, Faculty of Health Sciences, The University of Western Ontario, London, ON, N6A 5C1, Canada

    Daniel J. Belliveau

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  1. Melissa Morley
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  2. Claire Jones
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  3. Mandeep Sidhu
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  4. Vishal Gupta
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  5. Suzanne M. Bernier
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  7. Daniel J. Belliveau
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Correspondence to Daniel J. Belliveau.

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Funding was provided through the Natural Sciences and Engineering Research Council of Canada (D.J.B., W.J.R.) and Canadian Institutes of Health Research (S.M.B.). Initial work was supported by a Hargreaves foundation studentship to M.M. and a Natural Sciences and Engineering Research Council Undergraduate award to M.M. and C.J.

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Morley, M., Jones, C., Sidhu, M. et al. PKC inhibition increases gap junction intercellular communication and cell adhesion in human neuroblastoma. Cell Tissue Res 340, 229–242 (2010). https://doi.org/10.1007/s00441-010-0938-z

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