NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression
Summary: Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that...
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015778 |
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| author | Wenchao Xu Jianzhou Liu Qiaofei Liu Jia Xu Li Zhou Zhiyong Liang Haoran Huang Bowen Huang Gary Guishan Xiao Junchao Guo |
| author_facet | Wenchao Xu Jianzhou Liu Qiaofei Liu Jia Xu Li Zhou Zhiyong Liang Haoran Huang Bowen Huang Gary Guishan Xiao Junchao Guo |
| author_sort | Wenchao Xu |
| collection | DOAJ |
| description | Summary: Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor. We identified neutrophils_S100A12 (S100 calcium binding protein A12) cells as the pivotal pro-metastatic cluster, specifically distributed at the invasive front of the metastatic lesions. Mechanistically, our findings indicated that nuclear factor erythroid 2 (NFE2) is a key transcription factor regulating neutrophil phenotypic polarization. Metastatic tumors produce transforming growth factor β to activate the SMAD3 pathway within neutrophils, inducing NFE2-driven polarization. NFE2 promotes the transcription of peptidylarginine deiminase 4 by binding to its promoter, leading to the generation of neutrophil extracellular traps at the invasive front. Collectively, our data demonstrate that NFE2-driven neutrophil polarization is a potential target for anti-metastatic therapy. |
| format | Article |
| id | doaj-art-f02d8ca4d6aa467f8fb01d1f31f606ae |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-f02d8ca4d6aa467f8fb01d1f31f606ae2025-01-20T04:17:23ZengElsevierCell Reports2211-12472025-02-01442115226NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progressionWenchao Xu0Jianzhou Liu1Qiaofei Liu2Jia Xu3Li Zhou4Zhiyong Liang5Haoran Huang6Bowen Huang7Gary Guishan Xiao8Junchao Guo9Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China; National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China; National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China; National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaState Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China; National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaDepartment of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China; National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; School of Medicine, Tsinghua University, Beijing 100730, ChinaDepartment of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, ChinaState Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100730, China; National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing 100730, China; State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Corresponding authorSummary: Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor. We identified neutrophils_S100A12 (S100 calcium binding protein A12) cells as the pivotal pro-metastatic cluster, specifically distributed at the invasive front of the metastatic lesions. Mechanistically, our findings indicated that nuclear factor erythroid 2 (NFE2) is a key transcription factor regulating neutrophil phenotypic polarization. Metastatic tumors produce transforming growth factor β to activate the SMAD3 pathway within neutrophils, inducing NFE2-driven polarization. NFE2 promotes the transcription of peptidylarginine deiminase 4 by binding to its promoter, leading to the generation of neutrophil extracellular traps at the invasive front. Collectively, our data demonstrate that NFE2-driven neutrophil polarization is a potential target for anti-metastatic therapy.http://www.sciencedirect.com/science/article/pii/S2211124724015778CP: CancerCP: Immunology |
| spellingShingle | Wenchao Xu Jianzhou Liu Qiaofei Liu Jia Xu Li Zhou Zhiyong Liang Haoran Huang Bowen Huang Gary Guishan Xiao Junchao Guo NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression Cell Reports CP: Cancer CP: Immunology |
| title | NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression |
| title_full | NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression |
| title_fullStr | NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression |
| title_full_unstemmed | NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression |
| title_short | NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression |
| title_sort | nfe2 driven neutrophil polarization promotes pancreatic cancer liver metastasis progression |
| topic | CP: Cancer CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015778 |
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