PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway
ABSTRACT Background Platelet‐derived growth factor‐D (PDGF‐D) is expressed at high levels in various tumors and is involved in epithelial–mesenchymal transition (EMT) and the malignant behavior of cancer cells. However, its role in glioma progression and the underlying molecular mechanisms remain un...
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| Format: | Article |
| Language: | English |
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Wiley
2025-06-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.71002 |
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| author | Yao Li Yao Zhao Minghao Shi Xiaoshan Ma Mingbo Jia Zhongjun Shen Xiaoyi Liu Yunqian Li Liyan Zhao |
| author_facet | Yao Li Yao Zhao Minghao Shi Xiaoshan Ma Mingbo Jia Zhongjun Shen Xiaoyi Liu Yunqian Li Liyan Zhao |
| author_sort | Yao Li |
| collection | DOAJ |
| description | ABSTRACT Background Platelet‐derived growth factor‐D (PDGF‐D) is expressed at high levels in various tumors and is involved in epithelial–mesenchymal transition (EMT) and the malignant behavior of cancer cells. However, its role in glioma progression and the underlying molecular mechanisms remain unclear. Methods We used data from the Chinese Glioma Genome Atlas to evaluate the correlation among PDGF‐D expression, tumor grade, and phenotype of glioma. The in situ expression of PDGF‐D in clinical glioma specimens was analyzed through immunohistochemistry. Colony formation assays and transwell assays were performed for functional evaluation of glioma cell lines with PDGF‐D knockdown or overexpression. Western blotting and RT‐qPCR were conducted to explore molecular mechanisms. Results PDGF‐D was significantly upregulated in high‐grade glioma and was associated with the malignant phenotype and poor prognosis. Knocking down PDGF‐D in the LN18 glioma cell line reduced the expression of phosphorylated p65 and NOTCH1 and inhibited clonal proliferation, migration, invasion, and the EMT program. In contrast, inhibiting p65 phosphorylation in glioma cells overexpressing PDGF‐D led to the downregulation of NOTCH1 and reversed EMT. Conclusion PDGF‐D promotes the invasion and migration of glioma cells by activating the NF‐κB/NOTCH1 pathway. |
| format | Article |
| id | doaj-art-ee9cebdb0e654e9fab12fa2010717bfa |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-ee9cebdb0e654e9fab12fa2010717bfa2025-08-20T03:24:03ZengWileyCancer Medicine2045-76342025-06-011412n/an/a10.1002/cam4.71002PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 PathwayYao Li0Yao Zhao1Minghao Shi2Xiaoshan Ma3Mingbo Jia4Zhongjun Shen5Xiaoyi Liu6Yunqian Li7Liyan Zhao8Department of Blood Transfusion Second Hospital of Jilin University Changchun ChinaDepartment of Neurosurgery First Hospital of Jilin University Changchun ChinaDepartment of Blood Transfusion Second Hospital of Jilin University Changchun ChinaDepartment of Neurosurgery First Hospital of Jilin University Changchun ChinaDepartment of Blood Transfusion Second Hospital of Jilin University Changchun ChinaDepartment of Blood Transfusion Second Hospital of Jilin University Changchun ChinaDepartment of Blood Transfusion Second Hospital of Jilin University Changchun ChinaDepartment of Neurosurgery First Hospital of Jilin University Changchun ChinaDepartment of Blood Transfusion Second Hospital of Jilin University Changchun ChinaABSTRACT Background Platelet‐derived growth factor‐D (PDGF‐D) is expressed at high levels in various tumors and is involved in epithelial–mesenchymal transition (EMT) and the malignant behavior of cancer cells. However, its role in glioma progression and the underlying molecular mechanisms remain unclear. Methods We used data from the Chinese Glioma Genome Atlas to evaluate the correlation among PDGF‐D expression, tumor grade, and phenotype of glioma. The in situ expression of PDGF‐D in clinical glioma specimens was analyzed through immunohistochemistry. Colony formation assays and transwell assays were performed for functional evaluation of glioma cell lines with PDGF‐D knockdown or overexpression. Western blotting and RT‐qPCR were conducted to explore molecular mechanisms. Results PDGF‐D was significantly upregulated in high‐grade glioma and was associated with the malignant phenotype and poor prognosis. Knocking down PDGF‐D in the LN18 glioma cell line reduced the expression of phosphorylated p65 and NOTCH1 and inhibited clonal proliferation, migration, invasion, and the EMT program. In contrast, inhibiting p65 phosphorylation in glioma cells overexpressing PDGF‐D led to the downregulation of NOTCH1 and reversed EMT. Conclusion PDGF‐D promotes the invasion and migration of glioma cells by activating the NF‐κB/NOTCH1 pathway.https://doi.org/10.1002/cam4.71002EMTgliomaNF‐κBNOTCH1PDGF‐D |
| spellingShingle | Yao Li Yao Zhao Minghao Shi Xiaoshan Ma Mingbo Jia Zhongjun Shen Xiaoyi Liu Yunqian Li Liyan Zhao PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway Cancer Medicine EMT glioma NF‐κB NOTCH1 PDGF‐D |
| title | PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway |
| title_full | PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway |
| title_fullStr | PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway |
| title_full_unstemmed | PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway |
| title_short | PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway |
| title_sort | pdgf d promotes epithelial mesenchymal transition of glioma cells through the nf κb notch1 pathway |
| topic | EMT glioma NF‐κB NOTCH1 PDGF‐D |
| url | https://doi.org/10.1002/cam4.71002 |
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