Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas

Dormant cancer cells are starvation-resistant leading to problems in the management of cancer. In renal cell carcinomas (RCCs), starvation-resistant cells are resistant to various currently available therapies. However, targeting hypoxia inducible factor 2-alpha (HIF2-alpha) induces cell death in do...

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Autores principales: Isono, Takahiro, Chano, Tokuhiro, Yoshida, Tetsuya, Kageyama, Susumu, Kawauchi, Akihiro, Yonese, Junji, Yuasa, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955402/
https://www.ncbi.nlm.nih.gov/pubmed/29796174
http://dx.doi.org/10.18632/oncotarget.25214
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author Isono, Takahiro
Chano, Tokuhiro
Yoshida, Tetsuya
Kageyama, Susumu
Kawauchi, Akihiro
Yonese, Junji
Yuasa, Takeshi
author_facet Isono, Takahiro
Chano, Tokuhiro
Yoshida, Tetsuya
Kageyama, Susumu
Kawauchi, Akihiro
Yonese, Junji
Yuasa, Takeshi
author_sort Isono, Takahiro
collection PubMed
description Dormant cancer cells are starvation-resistant leading to problems in the management of cancer. In renal cell carcinomas (RCCs), starvation-resistant cells are resistant to various currently available therapies. However, targeting hypoxia inducible factor 2-alpha (HIF2-alpha) induces cell death in dormant-like/starvation-resistant RCCs. This study showed that the apoptotic cell death caused by tumor necrosis factor (TNF)-related apoptosis-induced ligand (TNFSF10/TRAIL) was attenuated by CASP8 and FADD-like apoptosis regulator (CFLAR/c-FLIP) following HIF2-alpha activation, despite the high expression of TRAIL in such RCCs. Knockdowns of TRAIL averted apoptotic cell death caused by HIF2-alpha inhibition in starvation-resistant RCCs. Knockdowns of both HIF2-alpha and c-FLIP augmented apoptotic cell death, whereas overexpression of c-FLIP completely averted apoptosis. In addition, high abundance of TRAIL was correlated with poor prognosis in patients with RCC, suggesting that TRAIL, followed by HIF2-alpha and c-FLIP, play a role in the survival and/or progression of malignant RCCs.
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spelling pubmed-59554022018-05-24 Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas Isono, Takahiro Chano, Tokuhiro Yoshida, Tetsuya Kageyama, Susumu Kawauchi, Akihiro Yonese, Junji Yuasa, Takeshi Oncotarget Research Paper Dormant cancer cells are starvation-resistant leading to problems in the management of cancer. In renal cell carcinomas (RCCs), starvation-resistant cells are resistant to various currently available therapies. However, targeting hypoxia inducible factor 2-alpha (HIF2-alpha) induces cell death in dormant-like/starvation-resistant RCCs. This study showed that the apoptotic cell death caused by tumor necrosis factor (TNF)-related apoptosis-induced ligand (TNFSF10/TRAIL) was attenuated by CASP8 and FADD-like apoptosis regulator (CFLAR/c-FLIP) following HIF2-alpha activation, despite the high expression of TRAIL in such RCCs. Knockdowns of TRAIL averted apoptotic cell death caused by HIF2-alpha inhibition in starvation-resistant RCCs. Knockdowns of both HIF2-alpha and c-FLIP augmented apoptotic cell death, whereas overexpression of c-FLIP completely averted apoptosis. In addition, high abundance of TRAIL was correlated with poor prognosis in patients with RCC, suggesting that TRAIL, followed by HIF2-alpha and c-FLIP, play a role in the survival and/or progression of malignant RCCs. Impact Journals LLC 2018-05-01 /pmc/articles/PMC5955402/ /pubmed/29796174 http://dx.doi.org/10.18632/oncotarget.25214 Text en Copyright: © 2018 Isono et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Isono, Takahiro
Chano, Tokuhiro
Yoshida, Tetsuya
Kageyama, Susumu
Kawauchi, Akihiro
Yonese, Junji
Yuasa, Takeshi
Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas
title Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas
title_full Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas
title_fullStr Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas
title_full_unstemmed Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas
title_short Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas
title_sort abundance of trail attenuated by hif2α and c-flip affects malignancy in renal cell carcinomas
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955402/
https://www.ncbi.nlm.nih.gov/pubmed/29796174
http://dx.doi.org/10.18632/oncotarget.25214
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