NFKB2 mediates colorectal cancer cell immune escape and metastasis in a STAT2/PD‐L1‐dependent manner
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| Format: | Artículo Open Access |
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2024
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| _version_ | 1867002602064969728 |
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| author | Jiwei Zhang Fen Ma Zhe Li Yuan Li Xun Sun Mingxu Song Fan Yang Enjiang Wu Xiaohui Wei Zhengtao Wang Li Yang |
| author_facet | Jiwei Zhang Fen Ma Zhe Li Yuan Li Xun Sun Mingxu Song Fan Yang Enjiang Wu Xiaohui Wei Zhengtao Wang Li Yang Jiwei Zhang Fen Ma Zhe Li Yuan Li Xun Sun Mingxu Song Fan Yang Enjiang Wu Xiaohui Wei Zhengtao Wang Li Yang |
| collection | Wiley Open Access |
| contents | NFKB2 mediates colorectal cancer cell immune escape and metastasis in a STAT2/PD‐L1‐dependent manner Jiwei Zhang Fen Ma Zhe Li Yuan Li Xun Sun Mingxu Song Fan Yang Enjiang Wu Xiaohui Wei Zhengtao Wang Li Yang MedComm AbstractThis study systematically analyzed the molecular mechanism and function of nuclear factor kappa B subunit 2 (NFKB2) in colorectal cancer (CRC) to investigate the potential of NFKB2 as a therapeutic target for CRC. Various experimental techniques, including RNA sequencing, proteome chip assays, and small molecule analysis, were used to obtain a deeper understanding of the regulation of NFKB2 in CRC. The results revealed that NFKB2 was upregulated in a significant proportion of patients with advanced hepatic metastasis of CRC. NFKB2 played an important role in promoting tumor growth through CD8+ T‐cell exhaustion. Moreover, NFKB2 directly interacted with signal transducer and activator of transcription 2 (STAT2), leading to increased phosphorylation of STAT2 and the upregulation of programmed death ligand 1 (PD‐L1). Applying a small molecule inhibitor of NFKB2 (Rg5) led to a reduction in PD‐L1 expression and improved response to programmed death‐1 blockade‐based immunotherapy. In conclusion, the facilitated NFKB2‐STAT2/PD‐L1 axis may suppress immune surveillance in CRC and targeting NFKB2 may enhance the efficacy of immunotherapeutic strategies. Our results provide novel insights into the molecular mechanisms underlying the contribution of NFKB2 in CRC immune escape. 10.1002/mco2.521 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/mco2.521 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_mco2_521 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | NFKB2 mediates colorectal cancer cell immune escape and metastasis in a STAT2/PD‐L1‐dependent manner Jiwei Zhang Fen Ma Zhe Li Yuan Li Xun Sun Mingxu Song Fan Yang Enjiang Wu Xiaohui Wei Zhengtao Wang Li Yang MedComm NFKB2 mediates colorectal cancer cell immune escape and metastasis in a STAT2/PD‐L1‐dependent manner Jiwei Zhang Fen Ma Zhe Li Yuan Li Xun Sun Mingxu Song Fan Yang Enjiang Wu Xiaohui Wei Zhengtao Wang Li Yang MedComm AbstractThis study systematically analyzed the molecular mechanism and function of nuclear factor kappa B subunit 2 (NFKB2) in colorectal cancer (CRC) to investigate the potential of NFKB2 as a therapeutic target for CRC. Various experimental techniques, including RNA sequencing, proteome chip assays, and small molecule analysis, were used to obtain a deeper understanding of the regulation of NFKB2 in CRC. The results revealed that NFKB2 was upregulated in a significant proportion of patients with advanced hepatic metastasis of CRC. NFKB2 played an important role in promoting tumor growth through CD8+ T‐cell exhaustion. Moreover, NFKB2 directly interacted with signal transducer and activator of transcription 2 (STAT2), leading to increased phosphorylation of STAT2 and the upregulation of programmed death ligand 1 (PD‐L1). Applying a small molecule inhibitor of NFKB2 (Rg5) led to a reduction in PD‐L1 expression and improved response to programmed death‐1 blockade‐based immunotherapy. In conclusion, the facilitated NFKB2‐STAT2/PD‐L1 axis may suppress immune surveillance in CRC and targeting NFKB2 may enhance the efficacy of immunotherapeutic strategies. Our results provide novel insights into the molecular mechanisms underlying the contribution of NFKB2 in CRC immune escape. 10.1002/mco2.521 http://creativecommons.org/licenses/by/4.0/ |
| title | NFKB2 mediates colorectal cancer cell immune escape and metastasis in a STAT2/PD‐L1‐dependent manner |
| topic | MedComm |
| url | https://onlinelibrary.wiley.com/doi/10.1002/mco2.521 |