Abstract |
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.
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Authors | Yongqing Heng, Yupei Liang, Junqian Zhang, Lihui Li, Wenjuan Zhang, Yanyu Jiang, Shiwen Wang, Lijun Jia |
Journal | Frontiers in oncology
(Front Oncol)
Vol. 11
Pg. 671180
( 2021)
ISSN: 2234-943X [Print] Switzerland |
PMID | 33898327
(Publication Type: Journal Article)
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Copyright | Copyright © 2021 Heng, Liang, Zhang, Li, Zhang, Jiang, Wang and Jia. |