Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axis
Abstract FER, an intracellular tyrosine kinase, is ubiquitously expressed in malignancies. However, the regulatory mechanisms of FER in diffuse large B-cell lymphoma (DLBCL) remain elusive. Here, we found that FER was upregulated in DLBCL, leading to unfavorable outcomes and increased tumorigenesis,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-01049-7 |
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| author | Jiarui Liu Yang Han Tiange Lu Dai Yuan Kang Lu Yiqing Cai Xiangxiang Zhou Xin Wang |
| author_facet | Jiarui Liu Yang Han Tiange Lu Dai Yuan Kang Lu Yiqing Cai Xiangxiang Zhou Xin Wang |
| author_sort | Jiarui Liu |
| collection | DOAJ |
| description | Abstract FER, an intracellular tyrosine kinase, is ubiquitously expressed in malignancies. However, the regulatory mechanisms of FER in diffuse large B-cell lymphoma (DLBCL) remain elusive. Here, we found that FER was upregulated in DLBCL, leading to unfavorable outcomes and increased tumorigenesis, as well as resistance to chemotherapy. While exposing cells to the FER inhibitor E260, cell proliferation and tumor growth were repressed. Moreover, greater tumor suppression resulted from combining exosome-E260 with chemotherapeutics compared with the suppression achieved by monotherapy. Mechanistically, E260 restored the activity of Hippo signaling by inhibiting AJUBA, resulting in YAP cytoplasmic sequestration. Furthermore, circulating exosomal FER may act as an indicator for the diagnosis and progression of DLBCL. In summary, FER could serve as a prognostic indicator and therapeutic target in DLBCL. Additionally, the application of exosomes in diagnosis or treatment may open up novel avenues for cancer therapy. |
| format | Article |
| id | doaj-art-1c0b0592785e403d8d3dd3fd1407283a |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-1c0b0592785e403d8d3dd3fd1407283a2025-08-20T03:42:29ZengNature Portfolionpj Precision Oncology2397-768X2025-07-019111210.1038/s41698-025-01049-7Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axisJiarui Liu0Yang Han1Tiange Lu2Dai Yuan3Kang Lu4Yiqing Cai5Xiangxiang Zhou6Xin Wang7Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityAbstract FER, an intracellular tyrosine kinase, is ubiquitously expressed in malignancies. However, the regulatory mechanisms of FER in diffuse large B-cell lymphoma (DLBCL) remain elusive. Here, we found that FER was upregulated in DLBCL, leading to unfavorable outcomes and increased tumorigenesis, as well as resistance to chemotherapy. While exposing cells to the FER inhibitor E260, cell proliferation and tumor growth were repressed. Moreover, greater tumor suppression resulted from combining exosome-E260 with chemotherapeutics compared with the suppression achieved by monotherapy. Mechanistically, E260 restored the activity of Hippo signaling by inhibiting AJUBA, resulting in YAP cytoplasmic sequestration. Furthermore, circulating exosomal FER may act as an indicator for the diagnosis and progression of DLBCL. In summary, FER could serve as a prognostic indicator and therapeutic target in DLBCL. Additionally, the application of exosomes in diagnosis or treatment may open up novel avenues for cancer therapy.https://doi.org/10.1038/s41698-025-01049-7 |
| spellingShingle | Jiarui Liu Yang Han Tiange Lu Dai Yuan Kang Lu Yiqing Cai Xiangxiang Zhou Xin Wang Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axis npj Precision Oncology |
| title | Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axis |
| title_full | Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axis |
| title_fullStr | Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axis |
| title_full_unstemmed | Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axis |
| title_short | Exosome- transported FER inhibitor suppresses progression of diffuse large B-cell lymphoma via regulating AJUBA/Hippo axis |
| title_sort | exosome transported fer inhibitor suppresses progression of diffuse large b cell lymphoma via regulating ajuba hippo axis |
| url | https://doi.org/10.1038/s41698-025-01049-7 |
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