Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability
Abstract Background The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer...
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2025-02-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-025-01358-1 |
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| author | Huiling Su Jie Shen Chenzi Gao Yue Zhao Wanyu Deng Bo Qin Xin Zhang Juan Lai Qian Wang Jie Dou Min Guo |
| author_facet | Huiling Su Jie Shen Chenzi Gao Yue Zhao Wanyu Deng Bo Qin Xin Zhang Juan Lai Qian Wang Jie Dou Min Guo |
| author_sort | Huiling Su |
| collection | DOAJ |
| description | Abstract Background The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer is not yet known. Epsin3 (EPN3), a member of the endocytic adaptor protein family, is essential for the endocytosis of multiple receptors. In this study, we aimed to investigate the role of EPN3 in modulating EGFR function, its effects on NSCLC progression, and its potential involvement in tyrosine kinase inhibitor (TKI) resistance, which remains a significant hurdle in NSCLC treatment. Results Our findings revealed that the expression of EPN3 is significantly up-regulated in NSCLC patients. Elevated EPN3 expression was proportional to shorter overall survival in patients with NSCLC. Functional analyses revealed that EPN3 directly interacts with EGFR, enhancing its recycling to the plasma membrane and preventing its degradation via the lysosomal pathway. This stabilization of EGFR led to sustained downstream signalling, promoting NSCLC cell proliferation and migration. Notably, mutations in the EGFR tyrosine kinase domain, which typically confer resistance to TKIs, did not alter the regulatory effect of EPN3. Conclusions EPN3 enhances EGFR signalling by promoting its recycling and stability, contributing to NSCLC progression and TKI resistance. Targeting EPN3 could offer a novel therapeutic strategy to overcome drug resistance in EGFR-driven NSCLC. |
| format | Article |
| id | doaj-art-41ef134eff0746b88d7b19874576e218 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-41ef134eff0746b88d7b19874576e2182025-02-09T12:56:21ZengBMCCell & Bioscience2045-37012025-02-0115111810.1186/s13578-025-01358-1Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stabilityHuiling Su0Jie Shen1Chenzi Gao2Yue Zhao3Wanyu Deng4Bo Qin5Xin Zhang6Juan Lai7Qian Wang8Jie Dou9Min Guo10State Key Laboratory of Natural Medicines, School of Life Science & Technology, Pharmaceutical UniversityState Key Laboratory of Natural Medicines, School of Life Science & Technology, Pharmaceutical UniversityKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical UniversityState Key Laboratory of Natural Medicines, School of Life Science & Technology, Pharmaceutical UniversityCollege of Life Science, Shangrao Normal UniversityShaoxing Women and Children’s HospitalGeneMind Biosciences Company LimitedGeneMind Biosciences Company LimitedKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical UniversityState Key Laboratory of Natural Medicines, School of Life Science & Technology, Pharmaceutical UniversityState Key Laboratory of Natural Medicines, School of Life Science & Technology, Pharmaceutical UniversityAbstract Background The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer is not yet known. Epsin3 (EPN3), a member of the endocytic adaptor protein family, is essential for the endocytosis of multiple receptors. In this study, we aimed to investigate the role of EPN3 in modulating EGFR function, its effects on NSCLC progression, and its potential involvement in tyrosine kinase inhibitor (TKI) resistance, which remains a significant hurdle in NSCLC treatment. Results Our findings revealed that the expression of EPN3 is significantly up-regulated in NSCLC patients. Elevated EPN3 expression was proportional to shorter overall survival in patients with NSCLC. Functional analyses revealed that EPN3 directly interacts with EGFR, enhancing its recycling to the plasma membrane and preventing its degradation via the lysosomal pathway. This stabilization of EGFR led to sustained downstream signalling, promoting NSCLC cell proliferation and migration. Notably, mutations in the EGFR tyrosine kinase domain, which typically confer resistance to TKIs, did not alter the regulatory effect of EPN3. Conclusions EPN3 enhances EGFR signalling by promoting its recycling and stability, contributing to NSCLC progression and TKI resistance. Targeting EPN3 could offer a novel therapeutic strategy to overcome drug resistance in EGFR-driven NSCLC.https://doi.org/10.1186/s13578-025-01358-1Non-small cell lung cancerEpsin3EGFRTKI resistance |
| spellingShingle | Huiling Su Jie Shen Chenzi Gao Yue Zhao Wanyu Deng Bo Qin Xin Zhang Juan Lai Qian Wang Jie Dou Min Guo Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability Cell & Bioscience Non-small cell lung cancer Epsin3 EGFR TKI resistance |
| title | Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability |
| title_full | Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability |
| title_fullStr | Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability |
| title_full_unstemmed | Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability |
| title_short | Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability |
| title_sort | epsin3 promotes non small cell lung cancer progression via modulating egfr stability |
| topic | Non-small cell lung cancer Epsin3 EGFR TKI resistance |
| url | https://doi.org/10.1186/s13578-025-01358-1 |
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