Small-molecule targeting of translation initiation for cancer therapy
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Author
Qiao, Yuan
Ozdelen, Esra
Schubert, Roland
Sevinc, Sema
Harbinski, Fred
Grubissich, Luciano
Singer, Samuel
Published Version
https://doi.org/10.18632/oncotarget.1186Metadata
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Aktas, Bertal H., Yuan Qiao, Esra Ozdelen, Roland Schubert, Sema Sevinc, Fred Harbinski, Luciano Grubissich, Samuel Singer, and Jose A. Halperin. 2013. “Small-molecule targeting of translation initiation for cancer therapy.” Oncotarget 4 (10): 1606-1617.Abstract
Translation initiation plays a critical role in the regulation of cell growth and tumorigenesis. We report here that inhibiting translation initiation through induction of eIF2α phosphorylation by small-molecular-weight compounds restricts the availability of the eIF2·GTP·Met-tRNAi ternary complex and abrogates the proliferation of cancer cells in vitro and tumor growth in vivo. Restricting the availability of the ternary complex preferentially down-regulates the expression of growth-promoting proteins and up-regulates the expression of ER stress response genes in cancer cells as well as in tumors excised from either animal models of human cancer or cancer patients. These findings provide the first direct evidence for translational control of gene-specific expression by small molecules in vivo and indicate that translation initiation factors are bona fide targets for development of mechanism-specific anti-cancer agents.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858549/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879348
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