PMID: 18719377Aug 23, 2008Paper

Targeting the eIF4F translation initiation complex for cancer therapy

Cell Cycle
Bruce W KonicekJeremy R Graff

Abstract

In multiple human cancers, the function of the eukaryotic translation initiation factor 4E (eIF4E) is elevated and directly related to disease progression. Overexpression or hyperactivation of eIF4E in experimental models can drive cellular transformation and malignant progression. Elevated eIF4E function triggers enhanced assembly of the eIF4F translation initiation complex and thereby drives cap-dependent translation. Though all capped mRNAs require eIF4F for translation, a pool of mRNAs are exceptionally dependent on elevated eIF4F activity for translation and are thereby selectively and disproportionately affected by altered eIF4F activity. These mRNAs encode proteins that play significant roles in all aspects of malignancy including angiogenesis factors (VEGF, FGF-2), onco-proteins (c-myc, cyclin D1, ODC), pro-survival proteins (survivin, BCL-2) and proteins involved in tumor invasion and metastasis (MMP-9, heparanase). Recent advances in targeting the eIF4F complex have highlighted the role for this complex in tumor cell survival and angiogenesis and have illuminated the enhanced susceptibility of the tumor cells to inhibition of the eIF4F complex. These studies have demonstrated the attractiveness and plausibility of tar...Continue Reading

Citations

Aug 13, 2013·Cancer Chemotherapy and Pharmacology·Juming YanYan Li
Mar 25, 2010·Nature Reviews. Cancer·Deborah SilveraRobert J Schneider
Apr 3, 2013·Molecular and Cellular Biology·Marie-Josée FournierRachid Mazroui
Sep 7, 2011·Therapy·Chiara Battelli, Daniel C Cho
Jan 19, 2016·Expert Reviews in Molecular Medicine·Chunwan LuYafei Cai
Nov 26, 2011·Ageing Research Reviews·Yulong HePeter J Hornsby
Jun 14, 2015·Cell Stress & Chaperones·Harvey SchwartzThomas Prince
Nov 1, 2015·Biochemical Society Transactions·Nadeem Siddiqui, Nahum Sonenberg
May 1, 2020·Cancer Cell International·Abdul Rouf WarAirong Qian
Aug 13, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew C Hsieh, Davide Ruggero
Feb 23, 2021·Advanced Healthcare Materials·Zheng-Rong LuNadia Ayat
Jul 12, 2013·Journal of Cell Science·Amanda M Preston, Linda M Hendershot
Apr 24, 2021·European Journal of Medicinal Chemistry·Xin JinTao Jiang

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