Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer
Abstract Background Dishevelled-associated activator of morphogenesis1 (DAAM1) is a member of the evolutionarily conserved Formin family and plays a significant role in the malignant progression of various human cancers. This study aims to explore the clinical and biological significance of DAAM1 in...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03631-8 |
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| author | Rui Xu Mengyun Wan Jiadong Pan Jie Mei Ji Zhou Yan Shen Jiayue Yang Yichao Zhu Jing Sun |
| author_facet | Rui Xu Mengyun Wan Jiadong Pan Jie Mei Ji Zhou Yan Shen Jiayue Yang Yichao Zhu Jing Sun |
| author_sort | Rui Xu |
| collection | DOAJ |
| description | Abstract Background Dishevelled-associated activator of morphogenesis1 (DAAM1) is a member of the evolutionarily conserved Formin family and plays a significant role in the malignant progression of various human cancers. This study aims to explore the clinical and biological significance of DAAM1 in pancreatic cancer. Methods Multiple public datasets and an in-house cohort were utilized to assess the clinical relevance of DAAM1 in pancreatic cancer. The LinkedOmics platform was employed to perform enrichment analysis of DAAM1-associated molecular pathways in pancreatic cancer. Subsequently, a series of in vitro and in vivo experiments were conducted to evaluate the biological roles of DAAM1 in pancreatic cancer cells and its effects on intratumoral T cells. Results DAAM1 was found to be upregulated in pancreatic cancer tissues, with higher expression levels observed in tumor cells. Additionally, high expression of DAAM1 was associated with poor prognosis. DAAM1 acted as an oncogene in pancreatic cancer, and its inhibition suppressed tumor cell proliferation, migration, and invasion, while promoted apoptosis. Furthermore, DAAM1 was involved in the JAK1/STAT1 signaling pathway and regulated PD-L1 expression in pancreatic cancer cells. The inhibition of DAAM1 also significantly reduced the exhaustion levels of CD8+ T cells. Conclusion In conclusion, DAAM1 functions as an oncogene and is immunologically implicated in pancreatic cancer, these findings suggest that DAAM1 may serve as a promising therapeutic target for the clinical management of pancreatic cancer. |
| format | Article |
| id | doaj-art-61e71db65ed946779c9cd4857a85a8f3 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-61e71db65ed946779c9cd4857a85a8f32025-02-02T12:43:26ZengBMCCancer Cell International1475-28672025-01-0125111410.1186/s12935-024-03631-8Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancerRui Xu0Mengyun Wan1Jiadong Pan2Jie Mei3Ji Zhou4Yan Shen5Jiayue Yang6Yichao Zhu7Jing Sun8Department of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartments of Gastroenterology, The Third People’s Hospital of KunshanDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartments of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi Medical Center, Nanjing Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background Dishevelled-associated activator of morphogenesis1 (DAAM1) is a member of the evolutionarily conserved Formin family and plays a significant role in the malignant progression of various human cancers. This study aims to explore the clinical and biological significance of DAAM1 in pancreatic cancer. Methods Multiple public datasets and an in-house cohort were utilized to assess the clinical relevance of DAAM1 in pancreatic cancer. The LinkedOmics platform was employed to perform enrichment analysis of DAAM1-associated molecular pathways in pancreatic cancer. Subsequently, a series of in vitro and in vivo experiments were conducted to evaluate the biological roles of DAAM1 in pancreatic cancer cells and its effects on intratumoral T cells. Results DAAM1 was found to be upregulated in pancreatic cancer tissues, with higher expression levels observed in tumor cells. Additionally, high expression of DAAM1 was associated with poor prognosis. DAAM1 acted as an oncogene in pancreatic cancer, and its inhibition suppressed tumor cell proliferation, migration, and invasion, while promoted apoptosis. Furthermore, DAAM1 was involved in the JAK1/STAT1 signaling pathway and regulated PD-L1 expression in pancreatic cancer cells. The inhibition of DAAM1 also significantly reduced the exhaustion levels of CD8+ T cells. Conclusion In conclusion, DAAM1 functions as an oncogene and is immunologically implicated in pancreatic cancer, these findings suggest that DAAM1 may serve as a promising therapeutic target for the clinical management of pancreatic cancer.https://doi.org/10.1186/s12935-024-03631-8DAAM1PD-L1JAK1/STAT1Pancreatic cancerT cells |
| spellingShingle | Rui Xu Mengyun Wan Jiadong Pan Jie Mei Ji Zhou Yan Shen Jiayue Yang Yichao Zhu Jing Sun Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer Cancer Cell International DAAM1 PD-L1 JAK1/STAT1 Pancreatic cancer T cells |
| title | Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer |
| title_full | Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer |
| title_fullStr | Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer |
| title_full_unstemmed | Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer |
| title_short | Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer |
| title_sort | formin protein daam1 positively regulates pd l1 expression via mediating the jak1 stat1 axis in pancreatic cancer |
| topic | DAAM1 PD-L1 JAK1/STAT1 Pancreatic cancer T cells |
| url | https://doi.org/10.1186/s12935-024-03631-8 |
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