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Decreased eIF3e/Int6 expression causes epithelial-to-mesenchymal transition in breast epithelial cells

Oncogene volume 32, pages 3598–3605 (2013)Cite this article

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Abstract

eIF3e/Int6 is a component of the multi-subunit eIF3 complex, which binds directly to the 40S ribosome to facilitate ribosome recruitment to mRNA and hence protein synthesis. Reduced expression of eIF3e/Int6 has been found in up to 37% of human breast cancers, and expression of a truncated mutant version of the mouse eIF3e/Int6 protein leads to malignant transformation of normal mammary cells. These findings suggest that eIF3e/Int6 is a tumor suppressor; however, a recent study has reported that a reduction of eIF3e/Int6 expression in breast cancer cells leads to reduced translation of oncogenes, suggesting that eIF3e/Int6 may in fact have an oncogenic role in breast cancer. To gain a better understanding of the role of eIF3e/Int6 in breast cancer, we have examined the effects of decreased eIF3e/Int6 expression in an immortalized breast epithelial cell line, MCF-10A. Surprisingly, we find that decreased expression of eIF3e/Int6 causes breast epithelial cells to undergo epithelial-to-mesenchymal transition (EMT). We show that EMT induced by a decrease in eIF3e/Int6 expression imparts invasive and migratory properties to breast epithelial cells, suggesting that regulation of EMT by eIF3e/Int6 may have an important role in breast cancer metastasis. Furthermore, we show that reduced eIF3e/Int6 expression in breast epithelial cells causes a specific increase in the expression of the key EMT regulators Snail1 and Zeb2, which occurs at both the transcriptional and post-transcriptional levels. Together, our data indicate a novel role of eIF3e/Int6 in the regulation of EMT in breast epithelial cells and support a tumor suppressor role of eIF3e/Int6.

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Acknowledgements

We thank Dr Craig McCormick for the generous gift of the retroviral transduction system used in this study, Dr Anirban Ghosh for advice on confocal immunofluorescence microscopy and Dr Martin Holcik for critical comments on the manuscript. This research was supported by a grant to SML from the Canadian Breast Cancer Foundation–Atlantic Chapter. SML is a Senior Scientist of the Beatrice Hunter Cancer Research Institute and a Canadian Institutes of Health Research–Regional Partnerships Program New Investigator (RSH-108667).

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Authors and Affiliations

  1. Atlantic Cancer Research Institute, Hôtel-Dieu Pavilion, Moncton, New Brunswick, Canada

    L D Gillis & S M Lewis

  2. Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

    S M Lewis

  3. Department of Biology, University of New Brunswick (Saint John), Saint John, New Brunswick, Canada

    S M Lewis

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  1. L D Gillis
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Correspondence to S M Lewis.

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Gillis, L., Lewis, S. Decreased eIF3e/Int6 expression causes epithelial-to-mesenchymal transition in breast epithelial cells. Oncogene 32, 3598–3605 (2013). https://doi.org/10.1038/onc.2012.371

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