Oncotarget

Research Papers:

Key contribution of eIF4H-mediated translational control in tumor promotion

Charlotte Vaysse _, Céline Philippe, Yvan Martineau, Cathy Quelen, Corinne Hieblot, Claire Renaud, Yvan Nicaise, Aurore Desquesnes, Maria Pannese, Thomas Filleron, Ghislaine Escourrou, Malcolm Lawson, Robert C Rintoul, Marie Bernadette Delisle, Stéphane Pyronnet, Pierre Brousset, Hervé Prats and Christian Touriol

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:39924-39940. https://doi.org/10.18632/oncotarget.5442

Metrics: PDF 842 views  |   HTML 1116 views  |   ?  


Abstract

Charlotte Vaysse1,2, Céline Philippe1,2, Yvan Martineau1,2, Cathy Quelen1,2, Corinne Hieblot1,2, Claire Renaud3, Yvan Nicaise4, Aurore Desquesnes5, Maria Pannese6, Thomas Filleron7, Ghislaine Escourrou1,4, Malcolm Lawson8, Robert C. Rintoul9, Marie Bernadette Delisle1,4, Stéphane Pyronnet1,2, Pierre Brousset1,2,10, Hervé Prats1,2, Christian Touriol1,2

1INSERM U1037, CRCT, Cancer Research Center of Toulouse, Toulouse, France

2Toulouse University, Paul Sabatier, Toulouse, France

3Department of Thoracic Surgery, Rangueil-Larrey Hospital, Toulouse, France

4Department of Pathology, CHU Rangueil, Toulouse, France

5Inserm US006 Crefre, Toulouse, France

6San Raffaele Scientific Institute, Milano, Italy

7Clinical trial office–Cellule Biostatistique Institut Universitaire du Cancer Toulouse, Toulouse, France

8Department of Respiratory Medicine, Broomfield Hospital, Chelmsford, Essex, UK

9Department of Thoracic Oncology, Papworth Hospital, Cambridge, UK

10Department of Pathology, Institut Universitaire du Cancer, Toulouse, France

Correspondence to:

Christian Touriol, e-mail: christian.touriol@inserm.fr

Keywords: lung carcinoma, chemoresistance, translation initiation factor, eIF4H, IRES, helicase

Received: May 27, 2015     Accepted: October 03, 2015     Published: October 15, 2015

ABSTRACT

Dysregulated expression of translation initiation factors has been associated with carcinogenesis, but underlying mechanisms remains to be fully understood. Here we show that eIF4H (eukaryotic translation initiation factor 4H), an activator of the RNA helicase eIF4A, is overexpressed in lung carcinomas and predictive of response to chemotherapy. In lung cancer cells, depletion of eIF4H enhances sensitization to chemotherapy, decreases cell migration and inhibits tumor growth in vivo, in association with reduced translation of mRNA encoding cell-proliferation (c-Myc, cyclin D1) angiogenic (FGF-2) and anti-apoptotic factors (CIAP-1, BCL-xL). Conversely, each isoform of eIF4H acts as an oncogene in NIH3T3 cells by stimulating transformation, invasion, tumor growth and resistance to drug-induced apoptosis together with increased translation of IRES-containing or structured 5′UTR mRNAs. These results demonstrate that eIF4H plays a crucial role in translational control and can promote cellular transformation by preferentially regulating the translation of potent growth and survival factor mRNAs, indicating that eIF4H is a promising new molecular target for cancer therapy.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 5442