EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinoma
Abstract Tyrosine kinase inhibitors (TKIs) are a class of therapies used to target specific genetic mutations such as epidermal growth factor receptor (EGFR) mutations in cancer treatment. This study investigates the function of epithelial membrane protein 3 (EMP3) in EGFR–TKI resistance in lung ade...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02894-9 |
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| author | Chunyan Wang Mengting Xiong Yifei Zhu Kun Li Jian Ni |
| author_facet | Chunyan Wang Mengting Xiong Yifei Zhu Kun Li Jian Ni |
| author_sort | Chunyan Wang |
| collection | DOAJ |
| description | Abstract Tyrosine kinase inhibitors (TKIs) are a class of therapies used to target specific genetic mutations such as epidermal growth factor receptor (EGFR) mutations in cancer treatment. This study investigates the function of epithelial membrane protein 3 (EMP3) in EGFR–TKI resistance in lung adenocarcinoma (LUAD). Human LUAD cells HCC827 and H1975 were exposed to different doses of osimertinib or erlotinib to generate TKI-resistant cell lines. These cells exhibited increased expression of EMP3. EMP3 overexpression in parental cells significantly increased TKI resistance, as well as promoted proliferation, migration, and stem cell characteristics. Epithelial–mesenchymal transition (EMT) is a major cause for EMP3 upregulation, as overexpression of ZEB1 increased EMP3 expression. By contrast, inhibition of the TGF/β signaling with LY2109761 reduced EMP3 expression in cells. In vivo, EMP3-overexpressing mouse 3LL cells exhibited strengthened tumorigenic activity in C57BL/6 mice in the presence of osimertinib treatment, accompanied by increased stem cell markers. Notably, the LY2109761 treatment reduced TKI resistance and diminished expansion, migration, and stemness in cancer cells induced by EMP3 overexpression. In conclusion, this study indicates that EMP3, upregulated upon EMT, contributes to EGFR–TKI resistance in LUAD cells. |
| format | Article |
| id | doaj-art-15a35f8f753d4797ac4e1d091f18c78d |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-15a35f8f753d4797ac4e1d091f18c78d2025-08-20T03:46:00ZengBMCEuropean Journal of Medical Research2047-783X2025-07-0130111310.1186/s40001-025-02894-9EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinomaChunyan Wang0Mengting Xiong1Yifei Zhu2Kun Li3Jian Ni4Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Oncology, Shanghai Medical College of Fudan UniversityDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityDepartment of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji UniversityAbstract Tyrosine kinase inhibitors (TKIs) are a class of therapies used to target specific genetic mutations such as epidermal growth factor receptor (EGFR) mutations in cancer treatment. This study investigates the function of epithelial membrane protein 3 (EMP3) in EGFR–TKI resistance in lung adenocarcinoma (LUAD). Human LUAD cells HCC827 and H1975 were exposed to different doses of osimertinib or erlotinib to generate TKI-resistant cell lines. These cells exhibited increased expression of EMP3. EMP3 overexpression in parental cells significantly increased TKI resistance, as well as promoted proliferation, migration, and stem cell characteristics. Epithelial–mesenchymal transition (EMT) is a major cause for EMP3 upregulation, as overexpression of ZEB1 increased EMP3 expression. By contrast, inhibition of the TGF/β signaling with LY2109761 reduced EMP3 expression in cells. In vivo, EMP3-overexpressing mouse 3LL cells exhibited strengthened tumorigenic activity in C57BL/6 mice in the presence of osimertinib treatment, accompanied by increased stem cell markers. Notably, the LY2109761 treatment reduced TKI resistance and diminished expansion, migration, and stemness in cancer cells induced by EMP3 overexpression. In conclusion, this study indicates that EMP3, upregulated upon EMT, contributes to EGFR–TKI resistance in LUAD cells.https://doi.org/10.1186/s40001-025-02894-9EMP3EMTTGF/β signalingEGFR–TKI resistanceLUAD |
| spellingShingle | Chunyan Wang Mengting Xiong Yifei Zhu Kun Li Jian Ni EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinoma European Journal of Medical Research EMP3 EMT TGF/β signaling EGFR–TKI resistance LUAD |
| title | EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinoma |
| title_full | EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinoma |
| title_fullStr | EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinoma |
| title_full_unstemmed | EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinoma |
| title_short | EMP3 is upregulated upon epithelial–mesenchymal transition and contributes to EGFR–tyrosine kinase inhibitor resistance in lung adenocarcinoma |
| title_sort | emp3 is upregulated upon epithelial mesenchymal transition and contributes to egfr tyrosine kinase inhibitor resistance in lung adenocarcinoma |
| topic | EMP3 EMT TGF/β signaling EGFR–TKI resistance LUAD |
| url | https://doi.org/10.1186/s40001-025-02894-9 |
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