Serine protease modulation of dependence receptors and EMT protein expression

McNair, K. , Forrest, C. M., Vicenten, M. C.J., Darlington, L. G. and Stone, T. W. (2019) Serine protease modulation of dependence receptors and EMT protein expression. Cancer Biology and Therapy, 20(3), pp. 349-367. (doi: 10.1080/15384047.2018.1529109) (PMID:30403907) (PMCID:PMC6370372)

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Expression of the tumour suppressor Deleted in Colorectal Cancer (DCC) and the related protein neogenin is reduced by the mammalian serine protease chymotrypsin or the bacterial serine protease subtilisin, with increased cell migration. The present work examines whether these actions are associated with changes in the expression of cadherins, β-catenin and vimentin, established markers of the Epithelial-Mesenchymal Transition (EMT) which has been linked with cell migration and tumour metastasis. The results confirm the depletion of DCC and neogenin and show that chymotrypsin and subtilisin also reduce expression of β-catenin in acutely prepared tissue sections but not in human mammary adenocarcinoma MCF-7 or MDA-MB-231 cells cultured in normal media, or primary normal human breast cells. A loss of β-catenin was also seen in low serum media but transfecting cells with a dcc-containing plasmid induced resistance. E-cadherin was not consistently affected but vimentin was induced by low serum-containing media and was increased by serine proteases in MCF-7 and MDA-MB-231 cells in parallel with increased wound closure. Vimentin might contribute to the promotion of cell migration. The results suggest that changes in EMT proteins depend on the cells or tissues concerned and do not parallel the expression of DCC and neogenin. The increased cell migration induced by serine proteases is not consistently associated with the expression of the EMT proteins implying either that the increased migration may be independent of EMT or supporting the view that EMT is not itself consistently related to migration. (241).

Item Type:Articles
Additional Information:This work was supported by Epsom Medical Research.
Glasgow Author(s) Enlighten ID:Forrest, Dr Caroline and Stone, Professor Trevor and Mcnair, Dr Kara
Authors: McNair, K., Forrest, C. M., Vicenten, M. C.J., Darlington, L. G., and Stone, T. W.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Cancer Biology and Therapy
Publisher:Taylor & Francis
ISSN (Online):1555-8576
Published Online:07 November 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Cancer Biology and Therapy 20(3): 349-367
Publisher Policy:Reproduced under a Creative Commons License

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