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Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells
The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061413/ https://www.ncbi.nlm.nih.gov/pubmed/33898327 http://dx.doi.org/10.3389/fonc.2021.671180 |
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author | Heng, Yongqing Liang, Yupei Zhang, Junqian Li, Lihui Zhang, Wenjuan Jiang, Yanyu Wang, Shiwen Jia, Lijun |
author_facet | Heng, Yongqing Liang, Yupei Zhang, Junqian Li, Lihui Zhang, Wenjuan Jiang, Yanyu Wang, Shiwen Jia, Lijun |
author_sort | Heng, Yongqing |
collection | PubMed |
description | The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway. |
format | Online Article Text |
id | pubmed-8061413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80614132021-04-23 Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells Heng, Yongqing Liang, Yupei Zhang, Junqian Li, Lihui Zhang, Wenjuan Jiang, Yanyu Wang, Shiwen Jia, Lijun Front Oncol Oncology The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway. Frontiers Media S.A. 2021-04-08 /pmc/articles/PMC8061413/ /pubmed/33898327 http://dx.doi.org/10.3389/fonc.2021.671180 Text en Copyright © 2021 Heng, Liang, Zhang, Li, Zhang, Jiang, Wang and Jia https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Heng, Yongqing Liang, Yupei Zhang, Junqian Li, Lihui Zhang, Wenjuan Jiang, Yanyu Wang, Shiwen Jia, Lijun Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells |
title | Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells |
title_full | Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells |
title_fullStr | Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells |
title_full_unstemmed | Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells |
title_short | Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells |
title_sort | camptothecin inhibits neddylation to activate the protective autophagy through nf-κb/ampk/mtor/ulk1 axis in human esophageal cancer cells |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061413/ https://www.ncbi.nlm.nih.gov/pubmed/33898327 http://dx.doi.org/10.3389/fonc.2021.671180 |
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