Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE
Abstract Helicobacter pylori (H. pylori) infection is a well-established risk factor for gastric cancer, primarily due to its virulence factor, cytotoxin-associated gene A (CagA). Although PD-L1/PD-1-mediated immune evasion is critical in cancer development, the impact of CagA on PD-L1 regulation re...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-07318-w |
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| author | Sifan Liu Nan Zhang Xu Ji Shuyue Yang Zheng Zhao Peng Li |
| author_facet | Sifan Liu Nan Zhang Xu Ji Shuyue Yang Zheng Zhao Peng Li |
| author_sort | Sifan Liu |
| collection | DOAJ |
| description | Abstract Helicobacter pylori (H. pylori) infection is a well-established risk factor for gastric cancer, primarily due to its virulence factor, cytotoxin-associated gene A (CagA). Although PD-L1/PD-1-mediated immune evasion is critical in cancer development, the impact of CagA on PD-L1 regulation remains unclear. This study revealed that H. pylori CagA upregulated squalene epoxidase (SQLE) expression, a key enzyme in the cholesterol biosynthesis pathway. Elevated SQLE activity increased cellular palmitoyl-CoA levels, enhancing PD-L1 palmitoylation while decreasing its ubiquitination. This ultimately increases PD-L1 stability, suppressing T cell activity and facilitating immune evasion in gastric cancer. In summary, our findings highlight the crucial role of the CagA-SQLE-PD-L1 axis in gastric cancer progression, suggesting potential therapeutic strategies for targeting CagA-positive gastric cancer. |
| format | Article |
| id | doaj-art-bcf3dc25f3a24fe7bbe78b122fd5a09b |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-bcf3dc25f3a24fe7bbe78b122fd5a09b2025-01-19T12:40:49ZengNature Publishing GroupCell Death and Disease2041-48892025-01-0116111310.1038/s41419-024-07318-wHelicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLESifan Liu0Nan Zhang1Xu Ji2Shuyue Yang3Zheng Zhao4Peng Li5Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease CenterDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease CenterDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease CenterDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease CenterDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease CenterDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease CenterAbstract Helicobacter pylori (H. pylori) infection is a well-established risk factor for gastric cancer, primarily due to its virulence factor, cytotoxin-associated gene A (CagA). Although PD-L1/PD-1-mediated immune evasion is critical in cancer development, the impact of CagA on PD-L1 regulation remains unclear. This study revealed that H. pylori CagA upregulated squalene epoxidase (SQLE) expression, a key enzyme in the cholesterol biosynthesis pathway. Elevated SQLE activity increased cellular palmitoyl-CoA levels, enhancing PD-L1 palmitoylation while decreasing its ubiquitination. This ultimately increases PD-L1 stability, suppressing T cell activity and facilitating immune evasion in gastric cancer. In summary, our findings highlight the crucial role of the CagA-SQLE-PD-L1 axis in gastric cancer progression, suggesting potential therapeutic strategies for targeting CagA-positive gastric cancer.https://doi.org/10.1038/s41419-024-07318-w |
| spellingShingle | Sifan Liu Nan Zhang Xu Ji Shuyue Yang Zheng Zhao Peng Li Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE Cell Death and Disease |
| title | Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE |
| title_full | Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE |
| title_fullStr | Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE |
| title_full_unstemmed | Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE |
| title_short | Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE |
| title_sort | helicobacter pylori caga promotes gastric cancer immune escape by upregulating sqle |
| url | https://doi.org/10.1038/s41419-024-07318-w |
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