Cancer Research 2015-03-15

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, Wilson H Miller

Index: Cancer Res. 75(6) , 1102-12, (2015)

Full Text: HTML

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.©2015 American Association for Cancer Research.

Related Compounds

Structure Name/CAS No. Articles
Glycerol Structure Glycerol
CAS:56-81-5
Ethanol Structure Ethanol
CAS:64-17-5
sodium dodecyl sulfate Structure sodium dodecyl sulfate
CAS:151-21-3
Acrylamide Crystals Structure Acrylamide Crystals
CAS:79-06-1
acetic acid Structure acetic acid
CAS:64-19-7
Hematoxylin Structure Hematoxylin
CAS:517-28-2
Stanolone Structure Stanolone
CAS:521-18-6
acetic acid Structure acetic acid
CAS:1173022-32-6
Phenol red Structure Phenol red
CAS:143-74-8
Bromophenol Blue Structure Bromophenol Blue
CAS:115-39-9