Expression of protein kinase C gamma promotes cell migration in colon cancer

// Catríona M. Dowling 1, 2 , Sheri L. Hayes 1, 2 , James J. Phelan 3 , Mary Clare Cathcart 3 , Stephen P. Finn 4 , Brian Mehigan 5 , Paul McCormick 5 , John C. Coffey 1 , Jacintha O’Sullivan 3 and Patrick A. Kiely 1, 2 1 Graduate Entry Medical School, University of Limerick, Limerick, Ireland 2 Health Research Institute University of Limerick, Limerick, Ireland 3 Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James’s Hospital, Dublin, Ireland 4 Department of Histopathology, St James’s Hospital, Trinity College Dublin, Ireland 5 GEMS, St. James Hospital, Dublin, Ireland Correspondence to: Patrick A. Kiely, email: Patrick.Kiely@ul.ie Keywords: protein kinase C gamma, tumor promoter, colon cancer Received: September 30, 2016 Accepted: June 13, 2017 Published: July 01, 2017 ABSTRACT Despite extensive efforts, Protein Kinase Cs (PKCs) have proven to be an intractable target in cancer therapies. Traditionally it was accepted that PKCs act as tumour promoters, however new research suggests that PKCs may play an important role in the suppression of cancer. A challenge in targeting PKCs is the limited data available in patient samples. One of the PKC isozymes, PKC gamma, is thought to be present only in the brain and has been largely neglected in the context of cancer. Analysis of gene expression levels of PKC gamma in patient matched normal and colon cancer tissue samples revealed an up-regulation of the gene in the cancer tissue of 54% of the patients examined. Mechanistically we demonstrate that a reduction in the levels of PKC gamma in the colon cancer cells inhibits cell migration and foci formation. Further to this, we observe an increase in cell adhesion and proliferation following the reduction of PKC gamma levels in the cell. Thus, PKC gamma plays a key role in colon cancer; making it an important isozyme that needs to be reconsidered in the context of cancer therapies.