PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis
Background Despite a series of attempts during the last decades, the prognosis for esophageal squamous cell carcinoma (ESCC) remains poor. Although clinical immunotherapy trials have shown encouraging results, their benefits are limited. This study aims to identify novel targets for immunotherapy in...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/8/e012044.full |
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| author | Ning Ma Wei Chen Yu Chen Xiang Wang Bing Zhu Kai Ding Lin Qiu Jing-jing Li Jing-Yi Huang Xin Liang Yan-Jun Xiang Qian-Zhi Ni Zhi-Chao Liu Qian-Wen Zheng Yi-Kang Wang Hui-Jun Cao Ji Xia Sheng Xu Xiao-Song Qiu Xi-Ran Zhang Lingyun Long Zhi-Gang Li Fan Yao |
| author_facet | Ning Ma Wei Chen Yu Chen Xiang Wang Bing Zhu Kai Ding Lin Qiu Jing-jing Li Jing-Yi Huang Xin Liang Yan-Jun Xiang Qian-Zhi Ni Zhi-Chao Liu Qian-Wen Zheng Yi-Kang Wang Hui-Jun Cao Ji Xia Sheng Xu Xiao-Song Qiu Xi-Ran Zhang Lingyun Long Zhi-Gang Li Fan Yao |
| author_sort | Ning Ma |
| collection | DOAJ |
| description | Background Despite a series of attempts during the last decades, the prognosis for esophageal squamous cell carcinoma (ESCC) remains poor. Although clinical immunotherapy trials have shown encouraging results, their benefits are limited. This study aims to identify novel targets for immunotherapy in ESCC.Experimental design ESCC cell lines and mouse models were used to identify the tumor-promoting function of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) and evaluate the effect of blockade of CD24. RNA sequencing was performed to profile transcriptomic changes upon PPDPF deficiency. Fluorescence microscopy-based phagocytosis assay and flow cytometry were employed to analyze macrophage phagocytosis. Immunoblotting, glutathione S-transferase-pulldown assay and co-immunoprecipitation assay were conducted to investigate the mechanism underlying the tumor-promoting role of PPDPF in ESCC. Clinical samples were analyzed to further validate the findings from preclinical models.Results The expression of PPDPF was significantly upregulated in ESCC. Deficiency of PPDPF inhibited the development of ESCC in mice. Mechanistically, PPDPF interfered with the c-Myc-GSK3β interaction and enhanced the protein stability of c-Myc, which increased the expression of CD24 and therefore promoted immune escape from macrophage phagocytosis. Positive correlations between PPDPF, c-Myc, and CD24 were observed in clinical samples. Anti-CD24 monotherapy effectively inhibited the ESCC tumor growth in mice.Conclusions PPDPF acts as an oncoprotein in ESCC by positively regulating the c-Myc/CD24 axis. These findings provide a potential effective target for immunotherapy in ESCC. |
| format | Article |
| id | doaj-art-1bf47b8e677b4160b414d294b75aa2cc |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-1bf47b8e677b4160b414d294b75aa2cc2025-08-20T03:59:35ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-08-0113810.1136/jitc-2025-012044PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axisNing Ma0Wei Chen1Yu Chen2Xiang Wang3Bing Zhu4Kai Ding5Lin Qiu6Jing-jing Li7Jing-Yi Huang8Xin Liang9Yan-Jun Xiang10Qian-Zhi Ni11Zhi-Chao Liu12Qian-Wen Zheng13Yi-Kang Wang14Hui-Jun Cao15Ji Xia16Sheng Xu17Xiao-Song Qiu18Xi-Ran Zhang19Lingyun Long20Zhi-Gang Li21Fan Yao223 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China6 Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China7 Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province. Affiliated Hangzhou First People`s Hospital, West Lake University School of Medicine, Hangzhou, Zhejiang, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China5 Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China3 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China3 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China1 Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China3 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China8 College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, ChinaBackground Despite a series of attempts during the last decades, the prognosis for esophageal squamous cell carcinoma (ESCC) remains poor. Although clinical immunotherapy trials have shown encouraging results, their benefits are limited. This study aims to identify novel targets for immunotherapy in ESCC.Experimental design ESCC cell lines and mouse models were used to identify the tumor-promoting function of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) and evaluate the effect of blockade of CD24. RNA sequencing was performed to profile transcriptomic changes upon PPDPF deficiency. Fluorescence microscopy-based phagocytosis assay and flow cytometry were employed to analyze macrophage phagocytosis. Immunoblotting, glutathione S-transferase-pulldown assay and co-immunoprecipitation assay were conducted to investigate the mechanism underlying the tumor-promoting role of PPDPF in ESCC. Clinical samples were analyzed to further validate the findings from preclinical models.Results The expression of PPDPF was significantly upregulated in ESCC. Deficiency of PPDPF inhibited the development of ESCC in mice. Mechanistically, PPDPF interfered with the c-Myc-GSK3β interaction and enhanced the protein stability of c-Myc, which increased the expression of CD24 and therefore promoted immune escape from macrophage phagocytosis. Positive correlations between PPDPF, c-Myc, and CD24 were observed in clinical samples. Anti-CD24 monotherapy effectively inhibited the ESCC tumor growth in mice.Conclusions PPDPF acts as an oncoprotein in ESCC by positively regulating the c-Myc/CD24 axis. These findings provide a potential effective target for immunotherapy in ESCC.https://jitc.bmj.com/content/13/8/e012044.full |
| spellingShingle | Ning Ma Wei Chen Yu Chen Xiang Wang Bing Zhu Kai Ding Lin Qiu Jing-jing Li Jing-Yi Huang Xin Liang Yan-Jun Xiang Qian-Zhi Ni Zhi-Chao Liu Qian-Wen Zheng Yi-Kang Wang Hui-Jun Cao Ji Xia Sheng Xu Xiao-Song Qiu Xi-Ran Zhang Lingyun Long Zhi-Gang Li Fan Yao PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis Journal for ImmunoTherapy of Cancer |
| title | PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis |
| title_full | PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis |
| title_fullStr | PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis |
| title_full_unstemmed | PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis |
| title_short | PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis |
| title_sort | ppdpf promotes the progression of esophageal squamous cell carcinoma via c myc cd24 axis |
| url | https://jitc.bmj.com/content/13/8/e012044.full |
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