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eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells

Clusterin is a secretory heterodimeric glycoprotein and the overexpression of secretory clusterin (sCLU) promotes cancer cell proliferation and reduces chemosensitivity. Therefore, sCLU might be an effective target for anticancer therapy. In the current study, we identified eIF3f as a novel CLU-inte...

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Autores principales: Lee, Ji-Yeon, Kim, Hyun-Ji, Rho, Seung Bae, Lee, Seung-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951308/
https://www.ncbi.nlm.nih.gov/pubmed/26988917
http://dx.doi.org/10.18632/oncotarget.8105
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author Lee, Ji-Yeon
Kim, Hyun-Ji
Rho, Seung Bae
Lee, Seung-Hoon
author_facet Lee, Ji-Yeon
Kim, Hyun-Ji
Rho, Seung Bae
Lee, Seung-Hoon
author_sort Lee, Ji-Yeon
collection PubMed
description Clusterin is a secretory heterodimeric glycoprotein and the overexpression of secretory clusterin (sCLU) promotes cancer cell proliferation and reduces chemosensitivity. Therefore, sCLU might be an effective target for anticancer therapy. In the current study, we identified eIF3f as a novel CLU-interacting protein and demonstrated its novel function as a CLU inhibitor. The overexpression of eIF3f retarded cancer cell growth significantly and induced apoptosis. In addition, eIF3f interacted with the α-chain (1–227) of sCLU. This interaction blocked modification of psCLU, thereby decreasing the expression and secretion of α/β CLU. Consequently, the overexpression of eIF3f suppressed Akt and ERK signaling and subsequently depleted CLU expression. In addition, eIF3F stabilized p53, which increased the expression of p21 and Bax. Interestingly, the expression of Bax was increased without the activation of p53. eIF3f injected into a xenograft model of human cervical cancer in nude mice markedly inhibited tumor growth. The identification of this novel function of eIF3f as a sCLU inhibitor might open novel avenues for developing improved strategies for CLU-targeted anti-cancer therapies.
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spelling pubmed-49513082016-07-21 eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells Lee, Ji-Yeon Kim, Hyun-Ji Rho, Seung Bae Lee, Seung-Hoon Oncotarget Research Paper Clusterin is a secretory heterodimeric glycoprotein and the overexpression of secretory clusterin (sCLU) promotes cancer cell proliferation and reduces chemosensitivity. Therefore, sCLU might be an effective target for anticancer therapy. In the current study, we identified eIF3f as a novel CLU-interacting protein and demonstrated its novel function as a CLU inhibitor. The overexpression of eIF3f retarded cancer cell growth significantly and induced apoptosis. In addition, eIF3f interacted with the α-chain (1–227) of sCLU. This interaction blocked modification of psCLU, thereby decreasing the expression and secretion of α/β CLU. Consequently, the overexpression of eIF3f suppressed Akt and ERK signaling and subsequently depleted CLU expression. In addition, eIF3F stabilized p53, which increased the expression of p21 and Bax. Interestingly, the expression of Bax was increased without the activation of p53. eIF3f injected into a xenograft model of human cervical cancer in nude mice markedly inhibited tumor growth. The identification of this novel function of eIF3f as a sCLU inhibitor might open novel avenues for developing improved strategies for CLU-targeted anti-cancer therapies. Impact Journals LLC 2016-03-15 /pmc/articles/PMC4951308/ /pubmed/26988917 http://dx.doi.org/10.18632/oncotarget.8105 Text en Copyright: © 2016 Lee et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lee, Ji-Yeon
Kim, Hyun-Ji
Rho, Seung Bae
Lee, Seung-Hoon
eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells
title eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells
title_full eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells
title_fullStr eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells
title_full_unstemmed eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells
title_short eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells
title_sort eif3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951308/
https://www.ncbi.nlm.nih.gov/pubmed/26988917
http://dx.doi.org/10.18632/oncotarget.8105
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