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Therapeutics, Targets, and Chemical Biology

Genetic and Pharmacologic Inhibition of eIF4E Reduces Breast Cancer Cell Migration, Invasion, and Metastasis

Filippa Pettersson, Sonia V. del Rincon, Audrey Emond, Bonnie Huor, Elaine Ngan, Jonathan Ng, Monica C. Dobocan, Peter M. Siegel and Wilson H. Miller Jr
Filippa Pettersson
Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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Sonia V. del Rincon
Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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Audrey Emond
Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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Bonnie Huor
Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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Elaine Ngan
Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada.
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Jonathan Ng
Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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Monica C. Dobocan
Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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Peter M. Siegel
Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada.
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Wilson H. Miller
Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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  • For correspondence: wmiller@ldi.jgh.mcgill.ca
DOI: 10.1158/0008-5472.CAN-14-1996
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Abstract

The translation initiation factor eIF4E is an oncogene that is commonly overexpressed in primary breast cancers and metastases. In this article, we report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and potently suppresses breast tumor formation. Ribavirin administration blocked the growth of primary breast tumors in several murine models and reduced the development of lung metastases in an invasive model. Mechanistically, eIF4E silencing or blockade reduced the invasiveness and metastatic capability of breast cancer cells in a manner associated with decreased activity of matrix metalloproteinase (MMP)-3 and MMP-9. Furthermore, eIF4E silencing or ribavirin treatment suppressed features of epithelial-to-mesenchymal transition, a process crucial for metastasis. Our findings offer a preclinical rationale to explore broadening the clinical evaluation of ribavirin, currently being tested in patients with eIF4E-overexpressing leukemia, as a strategy to treat solid tumors such as metastatic breast cancer. Cancer Res; 75(6); 1–11. ©2014 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received July 10, 2014.
  • Revision received December 12, 2014.
  • Accepted December 22, 2014.
  • ©2014 American Association for Cancer Research.
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Published OnlineFirst March 3, 2015
doi: 10.1158/0008-5472.CAN-14-1996

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Genetic and Pharmacologic Inhibition of eIF4E Reduces Breast Cancer Cell Migration, Invasion, and Metastasis
Filippa Pettersson, Sonia V. del Rincon, Audrey Emond, Bonnie Huor, Elaine Ngan, Jonathan Ng, Monica C. Dobocan, Peter M. Siegel and Wilson H. Miller Jr
Cancer Res March 3 2015 DOI: 10.1158/0008-5472.CAN-14-1996

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Genetic and Pharmacologic Inhibition of eIF4E Reduces Breast Cancer Cell Migration, Invasion, and Metastasis
Filippa Pettersson, Sonia V. del Rincon, Audrey Emond, Bonnie Huor, Elaine Ngan, Jonathan Ng, Monica C. Dobocan, Peter M. Siegel and Wilson H. Miller Jr
Cancer Res March 3 2015 DOI: 10.1158/0008-5472.CAN-14-1996
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Cancer Research Online ISSN: 1538-7445
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