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Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis

Unfolded protein response (UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum (ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein (PrP) is a glycosylated cell s...

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Autores principales: Gao, Zhenxing, Peng, Min, Chen, Liang, Yang, Xiaowen, Li, Huan, Shi, Run, Wu, Guiru, Cai, Lili, Song, Qibin, Li, Chaoyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513834/
https://www.ncbi.nlm.nih.gov/pubmed/31020572
http://dx.doi.org/10.1007/s12250-019-00107-2
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author Gao, Zhenxing
Peng, Min
Chen, Liang
Yang, Xiaowen
Li, Huan
Shi, Run
Wu, Guiru
Cai, Lili
Song, Qibin
Li, Chaoyang
author_facet Gao, Zhenxing
Peng, Min
Chen, Liang
Yang, Xiaowen
Li, Huan
Shi, Run
Wu, Guiru
Cai, Lili
Song, Qibin
Li, Chaoyang
author_sort Gao, Zhenxing
collection PubMed
description Unfolded protein response (UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum (ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein (PrP) is a glycosylated cell surface protein that has been shown to be up-regulated in many cancer cells. Since PrP is a protein prone to misfolding, ER stress can result in under-glycosylated PrP, which in turn may activate ER stress. To assess whether ER stress leads to the production of under-glycosylated PrP and whether under-glycosylated PrP may contribute to ER stress thus leading to cancer cell apoptosis, we treated different cancer cells with brefeldin A (BFA), thapsigargin (Thps), and tunicamycin (TM). We found that although BFA, Thps, and TM treatment activated UPR, only ATF4 was consistently activated by these reagents, but not other branches of ER stress. However, the canonical PERK-eIF2α-ATF4 did not account for the observed activation of ATF4 in lung cancer cells. In addition, BFA, but neither Thps nor TM, significantly stimulated the expression of cytosolic PrP. Finally, we found that the levels of PrP contributed to anti-apoptosis activity of BFA-induced cancer cell death. Thus, the pathway of BFA-induced persistent ER stress may be targeted for lung and pancreatic cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00107-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-65138342019-05-28 Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis Gao, Zhenxing Peng, Min Chen, Liang Yang, Xiaowen Li, Huan Shi, Run Wu, Guiru Cai, Lili Song, Qibin Li, Chaoyang Virol Sin Research Article Unfolded protein response (UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum (ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein (PrP) is a glycosylated cell surface protein that has been shown to be up-regulated in many cancer cells. Since PrP is a protein prone to misfolding, ER stress can result in under-glycosylated PrP, which in turn may activate ER stress. To assess whether ER stress leads to the production of under-glycosylated PrP and whether under-glycosylated PrP may contribute to ER stress thus leading to cancer cell apoptosis, we treated different cancer cells with brefeldin A (BFA), thapsigargin (Thps), and tunicamycin (TM). We found that although BFA, Thps, and TM treatment activated UPR, only ATF4 was consistently activated by these reagents, but not other branches of ER stress. However, the canonical PERK-eIF2α-ATF4 did not account for the observed activation of ATF4 in lung cancer cells. In addition, BFA, but neither Thps nor TM, significantly stimulated the expression of cytosolic PrP. Finally, we found that the levels of PrP contributed to anti-apoptosis activity of BFA-induced cancer cell death. Thus, the pathway of BFA-induced persistent ER stress may be targeted for lung and pancreatic cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00107-2) contains supplementary material, which is available to authorized users. Springer Singapore 2019-04-24 /pmc/articles/PMC6513834/ /pubmed/31020572 http://dx.doi.org/10.1007/s12250-019-00107-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gao, Zhenxing
Peng, Min
Chen, Liang
Yang, Xiaowen
Li, Huan
Shi, Run
Wu, Guiru
Cai, Lili
Song, Qibin
Li, Chaoyang
Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis
title Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis
title_full Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis
title_fullStr Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis
title_full_unstemmed Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis
title_short Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis
title_sort prion protein protects cancer cells against endoplasmic reticulum stress induced apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513834/
https://www.ncbi.nlm.nih.gov/pubmed/31020572
http://dx.doi.org/10.1007/s12250-019-00107-2
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