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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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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. |
format | Online Article Text |
id | pubmed-4951308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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