{"title":"EphrinA2通过EphA2和FAK促进胶质瘤细胞的迁移和侵袭。","authors":"Nozomi Hirai, Sho Tamai, Toshiya Ichinose, Hemragul Sabit, Norihiko Saito, Satoshi Iwabuchi, Mitsutoshi Nakada","doi":"10.1186/s12935-025-03826-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>EphrinA2, a ligand of the Eph receptor tyrosine kinase family, is implicated in the malignant phenotypes of various cancer cells. However, its function in glioblastoma remains unclear. Therefore, this study aimed to investigate the function and molecular mechanisms of ephrinA2 in the glioblastoma cells.</p><p><strong>Methods: </strong>EphrinA2 expression in five glioma cell lines and 40 cases of glioblastoma tissue obtained at surgery was examined. Additionally, we examined the effects of ephrinA2 knockdown in the migration and invasion of glioma cells in vitro and in vivo. Moreover, western blotting was performed to elucidate the mechanisms of ephrinA2 in glioma cell invasion and migration.</p><p><strong>Results: </strong>QRT-PCR showed that ephrinA2 was highly expressed in T98G and SNB19 cells. EphrinA2 knockdown shortened cell protrusions and reduced the migration and invasion abilities of T98G and SNB19 cells, which was confirmed by time-lapse dynamic observations. Western blotting showed that ephrinA2 knockdown suppressed phosphorylation of FAK at Tyr861 and EphA2 at Ser897 in glioma cells. Moreover, immunohistochemical analysis of glioblastoma samples showed that glioma cell invasion into normal brain was significantly higher in the ephrinA2 high expression group than in the low expression group.</p><p><strong>Conclusion: </strong>EphrinA2 may be involved in promoting glioblastoma invasion by regulating FAK and EphA2 phosphorylation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"191"},"PeriodicalIF":6.0000,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102856/pdf/","citationCount":"0","resultStr":"{\"title\":\"EphrinA2 promotes glioma cell migration and invasion through EphA2 and FAK.\",\"authors\":\"Nozomi Hirai, Sho Tamai, Toshiya Ichinose, Hemragul Sabit, Norihiko Saito, Satoshi Iwabuchi, Mitsutoshi Nakada\",\"doi\":\"10.1186/s12935-025-03826-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>EphrinA2, a ligand of the Eph receptor tyrosine kinase family, is implicated in the malignant phenotypes of various cancer cells. However, its function in glioblastoma remains unclear. Therefore, this study aimed to investigate the function and molecular mechanisms of ephrinA2 in the glioblastoma cells.</p><p><strong>Methods: </strong>EphrinA2 expression in five glioma cell lines and 40 cases of glioblastoma tissue obtained at surgery was examined. Additionally, we examined the effects of ephrinA2 knockdown in the migration and invasion of glioma cells in vitro and in vivo. Moreover, western blotting was performed to elucidate the mechanisms of ephrinA2 in glioma cell invasion and migration.</p><p><strong>Results: </strong>QRT-PCR showed that ephrinA2 was highly expressed in T98G and SNB19 cells. EphrinA2 knockdown shortened cell protrusions and reduced the migration and invasion abilities of T98G and SNB19 cells, which was confirmed by time-lapse dynamic observations. Western blotting showed that ephrinA2 knockdown suppressed phosphorylation of FAK at Tyr861 and EphA2 at Ser897 in glioma cells. Moreover, immunohistochemical analysis of glioblastoma samples showed that glioma cell invasion into normal brain was significantly higher in the ephrinA2 high expression group than in the low expression group.</p><p><strong>Conclusion: </strong>EphrinA2 may be involved in promoting glioblastoma invasion by regulating FAK and EphA2 phosphorylation.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"191\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-05-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102856/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03826-7\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03826-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
EphrinA2 promotes glioma cell migration and invasion through EphA2 and FAK.
Background: EphrinA2, a ligand of the Eph receptor tyrosine kinase family, is implicated in the malignant phenotypes of various cancer cells. However, its function in glioblastoma remains unclear. Therefore, this study aimed to investigate the function and molecular mechanisms of ephrinA2 in the glioblastoma cells.
Methods: EphrinA2 expression in five glioma cell lines and 40 cases of glioblastoma tissue obtained at surgery was examined. Additionally, we examined the effects of ephrinA2 knockdown in the migration and invasion of glioma cells in vitro and in vivo. Moreover, western blotting was performed to elucidate the mechanisms of ephrinA2 in glioma cell invasion and migration.
Results: QRT-PCR showed that ephrinA2 was highly expressed in T98G and SNB19 cells. EphrinA2 knockdown shortened cell protrusions and reduced the migration and invasion abilities of T98G and SNB19 cells, which was confirmed by time-lapse dynamic observations. Western blotting showed that ephrinA2 knockdown suppressed phosphorylation of FAK at Tyr861 and EphA2 at Ser897 in glioma cells. Moreover, immunohistochemical analysis of glioblastoma samples showed that glioma cell invasion into normal brain was significantly higher in the ephrinA2 high expression group than in the low expression group.
Conclusion: EphrinA2 may be involved in promoting glioblastoma invasion by regulating FAK and EphA2 phosphorylation.
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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