| Title: |
Targeting NEDD8 suppresses surgical stress-facilitated metastasis of colon cancer via restraining regulatory T cells |
| Authors: |
Yi Jiang, Shenjia Gao, Hao Sun, Xinyi Wu, Jiahui Gu, Han Wu, Yun Liao, Ronen Ben-Ami, Changhong Miao, Rong Shen, Jinlong Liu, Wankun Chen |
| Source: |
Cell Death and Disease, Vol 15, Iss 1, Pp 1-13 (2024) |
| Publisher Information: |
Nature Publishing Group, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
Abstract Regulatory T cells (Tregs) are a key determinant for the immunosuppressive and premetastatic niche for cancer progression after surgery resection. However, the precise mechanisms regulating Tregs function during surgical stress-facilitated cancer metastasis remain unknown. This study aims to unravel the mechanisms and explore potential strategies for preventing surgical stress-induced metastasis by targeting NEDD8. Using a surgical stress mouse model, we found that surgical stress results in the increased expression of NEDD8 in Tregs. NEDD8 depletion abrogates postoperative lung metastasis of colon cancer cells by inhibiting Treg immunosuppression and thereby partially recovering CD8+T cell and NK cell-mediated anti-tumor immunity. Furthermore, Treg mitophagy and mitochondrial respiration exacerbated in surgically stressed mice were attenuated by NEDD8 depletion. Our observations suggest that cancer progression may result from surgery-induced enhancement of NEDD8 expression and the subsequent immunosuppressive function of Tregs. More importantly, depleting or inhibiting NEDD8 can be an efficient strategy to reduce cancer metastasis after surgery resection by regulating the function of Tregs. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-023-06396-6 |
| Access URL: |
https://doaj.org/article/cef74ff46a7d43c9a558360c656cf874 |
| Accession Number: |
edsdoj.f74ff46a7d43c9a558360c656cf874 |
| Database: |
Directory of Open Access Journals |
