S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory malignancies and has a poor prognosis. In recent years, increasing evidence has shown that an imbalance of metabolism may contribute to unrestricted pancreatic tumour progression and that the pentose phosphate pathway (PP...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-06-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05004-3 |
| _version_ | 1818257073635328000 |
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| author | Xue Zeng Hong Guo Zhuang Liu Zilan Qin Yuyang Cong Naihan Ren Yuxiang Zhang Na Zhang |
| author_facet | Xue Zeng Hong Guo Zhuang Liu Zilan Qin Yuyang Cong Naihan Ren Yuxiang Zhang Na Zhang |
| author_sort | Xue Zeng |
| collection | DOAJ |
| description | Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory malignancies and has a poor prognosis. In recent years, increasing evidence has shown that an imbalance of metabolism may contribute to unrestricted pancreatic tumour progression and that the pentose phosphate pathway (PPP) plays a pivotal role in cellular metabolism. S100A11 has been shown to regulate multiple biological functions related to the progression and metastasis of various cancer types. However, the exact mechanisms and prognostic value of S100A11 in PDAC remain unclear. Here, we found that S100A11 expression was increased in PDAC and significantly associated with worse prognosis and disease progression. Mechanistically, S100A11 knockdown suppressed the PPP by impairing nascent mRNA synthesis of TKT (transketolase). The current study also demonstrated that H3K4me3 at the −268/+77 region of the TKT promoter was required for its transcriptional activation and S100A11 promoted H3K4me3 loading to the TKT promoter by interacting with SMYD3 protein. Taking these findings together, this study provided new insights into the potential value of S100A11 for treating pancreatic cancer, suggesting that it could be a therapeutic target for PDAC patients. |
| first_indexed | 2024-12-12T17:37:51Z |
| format | Article |
| id | doaj.art-bdb409a2be44420e821811b0755ff9d6 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-12T17:37:51Z |
| publishDate | 2022-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-bdb409a2be44420e821811b0755ff9d62022-12-22T00:17:10ZengNature Publishing GroupCell Death and Disease2041-48892022-06-0113611310.1038/s41419-022-05004-3S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinomaXue Zeng0Hong Guo1Zhuang Liu2Zilan Qin3Yuyang Cong4Naihan Ren5Yuxiang Zhang6Na Zhang7Department of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyDepartment of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of TechnologyAbstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory malignancies and has a poor prognosis. In recent years, increasing evidence has shown that an imbalance of metabolism may contribute to unrestricted pancreatic tumour progression and that the pentose phosphate pathway (PPP) plays a pivotal role in cellular metabolism. S100A11 has been shown to regulate multiple biological functions related to the progression and metastasis of various cancer types. However, the exact mechanisms and prognostic value of S100A11 in PDAC remain unclear. Here, we found that S100A11 expression was increased in PDAC and significantly associated with worse prognosis and disease progression. Mechanistically, S100A11 knockdown suppressed the PPP by impairing nascent mRNA synthesis of TKT (transketolase). The current study also demonstrated that H3K4me3 at the −268/+77 region of the TKT promoter was required for its transcriptional activation and S100A11 promoted H3K4me3 loading to the TKT promoter by interacting with SMYD3 protein. Taking these findings together, this study provided new insights into the potential value of S100A11 for treating pancreatic cancer, suggesting that it could be a therapeutic target for PDAC patients.https://doi.org/10.1038/s41419-022-05004-3 |
| spellingShingle | Xue Zeng Hong Guo Zhuang Liu Zilan Qin Yuyang Cong Naihan Ren Yuxiang Zhang Na Zhang S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma Cell Death and Disease |
| title | S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma |
| title_full | S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma |
| title_fullStr | S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma |
| title_full_unstemmed | S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma |
| title_short | S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma |
| title_sort | s100a11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma |
| url | https://doi.org/10.1038/s41419-022-05004-3 |
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