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GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation
Given the dense stroma and poor vascularization, access to nutrients is limited in the microenvironment of pancreatic ductal adenocarcinoma (PDA). PDA cells can efficiently recycle various metabolic substrates through the activation of different rescuing pathways, including the autophagy pathway. Ho...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290009/ https://www.ncbi.nlm.nih.gov/pubmed/30538220 http://dx.doi.org/10.1038/s41419-018-1244-z |
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author | Meng, Qingcai Xu, Jin Liang, Chen Liu, Jiang Hua, Jie Zhang, Yiyin Ni, Quanxing Shi, Si Yu, Xianjun |
author_facet | Meng, Qingcai Xu, Jin Liang, Chen Liu, Jiang Hua, Jie Zhang, Yiyin Ni, Quanxing Shi, Si Yu, Xianjun |
author_sort | Meng, Qingcai |
collection | PubMed |
description | Given the dense stroma and poor vascularization, access to nutrients is limited in the microenvironment of pancreatic ductal adenocarcinoma (PDA). PDA cells can efficiently recycle various metabolic substrates through the activation of different rescuing pathways, including the autophagy pathway. However, the precise roles of autophagy in cancer metabolism are not yet fully understood. In the present study, we first monitored the effect of glucose deprivation on autophagy and on the expression of glutathione peroxidase-1 (GPx1) in PDA cells under the glucose-free environment. Glucose starvation induced progressive autophagy activation in PDA cells via the activation of ROS/AMPK signaling. GPx1 degradation caused by glucose deprivation led to further ROS-dependent autophagy activation. Both GPx1 overexpression and autophagy inhibition sensitized cells to starvation-induced cell death through the activation of caspase-dependent apoptosis. Moreover, GPx1 may regulate glycolysis inhibition in PDA cells under glucose-deprived conditions. In summary, this study increases our understanding of the role of GPx1 in the induction of protective autophagy in PDA cells under extreme glucose starvation and may provide new therapeutic targets or innovative therapies. |
format | Online Article Text |
id | pubmed-6290009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62900092018-12-12 GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation Meng, Qingcai Xu, Jin Liang, Chen Liu, Jiang Hua, Jie Zhang, Yiyin Ni, Quanxing Shi, Si Yu, Xianjun Cell Death Dis Article Given the dense stroma and poor vascularization, access to nutrients is limited in the microenvironment of pancreatic ductal adenocarcinoma (PDA). PDA cells can efficiently recycle various metabolic substrates through the activation of different rescuing pathways, including the autophagy pathway. However, the precise roles of autophagy in cancer metabolism are not yet fully understood. In the present study, we first monitored the effect of glucose deprivation on autophagy and on the expression of glutathione peroxidase-1 (GPx1) in PDA cells under the glucose-free environment. Glucose starvation induced progressive autophagy activation in PDA cells via the activation of ROS/AMPK signaling. GPx1 degradation caused by glucose deprivation led to further ROS-dependent autophagy activation. Both GPx1 overexpression and autophagy inhibition sensitized cells to starvation-induced cell death through the activation of caspase-dependent apoptosis. Moreover, GPx1 may regulate glycolysis inhibition in PDA cells under glucose-deprived conditions. In summary, this study increases our understanding of the role of GPx1 in the induction of protective autophagy in PDA cells under extreme glucose starvation and may provide new therapeutic targets or innovative therapies. Nature Publishing Group UK 2018-12-11 /pmc/articles/PMC6290009/ /pubmed/30538220 http://dx.doi.org/10.1038/s41419-018-1244-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Meng, Qingcai Xu, Jin Liang, Chen Liu, Jiang Hua, Jie Zhang, Yiyin Ni, Quanxing Shi, Si Yu, Xianjun GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation |
title | GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation |
title_full | GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation |
title_fullStr | GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation |
title_full_unstemmed | GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation |
title_short | GPx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation |
title_sort | gpx1 is involved in the induction of protective autophagy in pancreatic cancer cells in response to glucose deprivation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290009/ https://www.ncbi.nlm.nih.gov/pubmed/30538220 http://dx.doi.org/10.1038/s41419-018-1244-z |
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