YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape
Abstract Lactate is a major metabolic product of tumor cells in microenvironment. Increasing evidence has indicated that lactate accumulation could alter the immune response in human cancers, including cervical cancer. However, the function and significance of N6-methyladenosine (m6A) reader YTHDF1...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-07128-0 |
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| author | Jing Xiong Ling He Xiaoshan Chai Yongjing Zhang Shujuan Sun |
| author_facet | Jing Xiong Ling He Xiaoshan Chai Yongjing Zhang Shujuan Sun |
| author_sort | Jing Xiong |
| collection | DOAJ |
| description | Abstract Lactate is a major metabolic product of tumor cells in microenvironment. Increasing evidence has indicated that lactate accumulation could alter the immune response in human cancers, including cervical cancer. However, the function and significance of N6-methyladenosine (m6A) reader YTHDF1 in cervical cancer cells’ lactate metabolism and immunotherapy remain obscure. Results illustrated that YTHDF1 predicted unfavorable clinical outcomes of cervical cancer, which was negatively correlated with CD8+ T cell infiltration. In the co-culture of tumor cells with CD8+ T cells, YTHDF1 overexpression promoted the lactate accumulation and attenuated the cytotoxic CD8+ T cell’s killing effect. Correspondingly, YTHDF1 knockdown exerted the opposite effects. Mechanistically, YTHDF1 targeted the m6A site on SLC16A1 gene (MCT1) to determine its fate. YTHDF1 upregulated MCT1 expression by enhancing MCT1 stability mediated by m6A-modified manner. Collectively, our results revealed an oncogenic role played by YTHDF1 in cervical cancer through m6A/MCT1-dependent manner. In conclusion, these findings unveil the immune escape-promoting effect of YTHDF1 in cervical cancer by boosting the lactate accumulation, which might illuminate a novel target for more precise immunotherapy. |
| format | Article |
| id | doaj-art-a57d2ca0a93a4e9f98224d86b82f789b |
| institution | OA Journals |
| issn | 2041-4889 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-a57d2ca0a93a4e9f98224d86b82f789b2025-08-20T02:33:06ZengNature Publishing GroupCell Death and Disease2041-48892024-11-01151111110.1038/s41419-024-07128-0YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escapeJing Xiong0Ling He1Xiaoshan Chai2Yongjing Zhang3Shujuan Sun4Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South UniversityDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South UniversityDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South UniversityDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South UniversityDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South UniversityAbstract Lactate is a major metabolic product of tumor cells in microenvironment. Increasing evidence has indicated that lactate accumulation could alter the immune response in human cancers, including cervical cancer. However, the function and significance of N6-methyladenosine (m6A) reader YTHDF1 in cervical cancer cells’ lactate metabolism and immunotherapy remain obscure. Results illustrated that YTHDF1 predicted unfavorable clinical outcomes of cervical cancer, which was negatively correlated with CD8+ T cell infiltration. In the co-culture of tumor cells with CD8+ T cells, YTHDF1 overexpression promoted the lactate accumulation and attenuated the cytotoxic CD8+ T cell’s killing effect. Correspondingly, YTHDF1 knockdown exerted the opposite effects. Mechanistically, YTHDF1 targeted the m6A site on SLC16A1 gene (MCT1) to determine its fate. YTHDF1 upregulated MCT1 expression by enhancing MCT1 stability mediated by m6A-modified manner. Collectively, our results revealed an oncogenic role played by YTHDF1 in cervical cancer through m6A/MCT1-dependent manner. In conclusion, these findings unveil the immune escape-promoting effect of YTHDF1 in cervical cancer by boosting the lactate accumulation, which might illuminate a novel target for more precise immunotherapy.https://doi.org/10.1038/s41419-024-07128-0 |
| spellingShingle | Jing Xiong Ling He Xiaoshan Chai Yongjing Zhang Shujuan Sun YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape Cell Death and Disease |
| title | YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape |
| title_full | YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape |
| title_fullStr | YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape |
| title_full_unstemmed | YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape |
| title_short | YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape |
| title_sort | ythdf1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape |
| url | https://doi.org/10.1038/s41419-024-07128-0 |
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