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eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest

Aberrantly activated mechanistic target of rapamycin (mTOR) signaling pathway stimulates translation initiation/protein synthesis and eventually causes tumors. Targeting these processes thus holds potential for treating mTOR-associated diseases. We tested the potential of eFT226, a sequence-selectiv...

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Detalles Bibliográficos
Autores principales: Han, Luyang, Wu, Yuting, Liu, Fangming, Zhang, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266907/
https://www.ncbi.nlm.nih.gov/pubmed/35805935
http://dx.doi.org/10.3390/ijms23136932
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author Han, Luyang
Wu, Yuting
Liu, Fangming
Zhang, Hongbing
author_facet Han, Luyang
Wu, Yuting
Liu, Fangming
Zhang, Hongbing
author_sort Han, Luyang
collection PubMed
description Aberrantly activated mechanistic target of rapamycin (mTOR) signaling pathway stimulates translation initiation/protein synthesis and eventually causes tumors. Targeting these processes thus holds potential for treating mTOR-associated diseases. We tested the potential of eFT226, a sequence-selective inhibitor of eIF4A-mediated translation, in the treatment of mTOR hyperactive cells caused by the deletion of tuberous sclerosis complex 1/2 (TSC1/2) or phosphatase and TENsin homology (PTEN). eFT226 preferentially inhibited the proliferation of Tsc2- and Pten-deficient cells by inducing necroptosis and G2/M phase arrest. In addition, eFT226 blocked the development of TSC2-deficient tumors. The translation initiation inhibitor is thus a promising regimen for the treatment of hyperactive mTOR-mediated tumors.
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spelling pubmed-92669072022-07-09 eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest Han, Luyang Wu, Yuting Liu, Fangming Zhang, Hongbing Int J Mol Sci Article Aberrantly activated mechanistic target of rapamycin (mTOR) signaling pathway stimulates translation initiation/protein synthesis and eventually causes tumors. Targeting these processes thus holds potential for treating mTOR-associated diseases. We tested the potential of eFT226, a sequence-selective inhibitor of eIF4A-mediated translation, in the treatment of mTOR hyperactive cells caused by the deletion of tuberous sclerosis complex 1/2 (TSC1/2) or phosphatase and TENsin homology (PTEN). eFT226 preferentially inhibited the proliferation of Tsc2- and Pten-deficient cells by inducing necroptosis and G2/M phase arrest. In addition, eFT226 blocked the development of TSC2-deficient tumors. The translation initiation inhibitor is thus a promising regimen for the treatment of hyperactive mTOR-mediated tumors. MDPI 2022-06-22 /pmc/articles/PMC9266907/ /pubmed/35805935 http://dx.doi.org/10.3390/ijms23136932 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Luyang
Wu, Yuting
Liu, Fangming
Zhang, Hongbing
eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest
title eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest
title_full eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest
title_fullStr eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest
title_full_unstemmed eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest
title_short eIF4A1 Inhibitor Suppresses Hyperactive mTOR-Associated Tumors by Inducing Necroptosis and G2/M Arrest
title_sort eif4a1 inhibitor suppresses hyperactive mtor-associated tumors by inducing necroptosis and g2/m arrest
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266907/
https://www.ncbi.nlm.nih.gov/pubmed/35805935
http://dx.doi.org/10.3390/ijms23136932
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