The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancer
Abstract Paclitaxel combination therapy is the main chemotherapy regimen for endometrial cancer (EC); however, subsequent drug resistance is a bottleneck limiting its widespread clinical application. We found that human insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was abnormally ele...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08065-0 |
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| author | Yidong Ge Lili Kong Yuxuan Li Zongdong Yu Fengguang Zhai Ziqing Zhan Gun Chen Shuyan Wang Haoyun Wang Yuxuan Wang Jianan Zhao Lechen Hu Jianing Mao Siyuan Wang Jiaxin Shi Mengxiang Zhao Pengrong Lou Meng Ye Xiaofeng Jin |
| author_facet | Yidong Ge Lili Kong Yuxuan Li Zongdong Yu Fengguang Zhai Ziqing Zhan Gun Chen Shuyan Wang Haoyun Wang Yuxuan Wang Jianan Zhao Lechen Hu Jianing Mao Siyuan Wang Jiaxin Shi Mengxiang Zhao Pengrong Lou Meng Ye Xiaofeng Jin |
| author_sort | Yidong Ge |
| collection | DOAJ |
| description | Abstract Paclitaxel combination therapy is the main chemotherapy regimen for endometrial cancer (EC); however, subsequent drug resistance is a bottleneck limiting its widespread clinical application. We found that human insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was abnormally elevated in paclitaxel-resistant EC cells and confirmed that the reduction of IGF2BP3 can effectively improve the sensitivity of EC cells to paclitaxel in vitro and in vivo. Mechanistically, elevated IGF2BP3 promotes the half-life of c-Myc by competitively inhibiting Speckle-type POZ protein (SPOP)-mediated ubiquitination and degradation of c-Myc. As a transcription factor, c-Myc can bind to the promoter of IGF2BP3, thus contributing to the increased transcription of IGF2BP3 via positive feedback and forming a signaling loop that ultimately causes the accumulation of c-Myc-induced paclitaxel resistance. Based on these findings, the application of c-Myc inhibitors (10058-F4) combined with paclitaxel helped paclitaxel-resistant EC cells regain paclitaxel sensitivity in vitro and in vivo. Together, we reveal the underlying mechanism of paclitaxel resistance in endometrial cancer cells and provide insights into treatment strategies for paclitaxel-resistant EC patients. |
| format | Article |
| id | doaj-art-da3a9294f1ed4b1a99e30aa4f6f1fb6b |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-da3a9294f1ed4b1a99e30aa4f6f1fb6b2025-08-20T04:01:40ZengNature PortfolioCommunications Biology2399-36422025-04-018111510.1038/s42003-025-08065-0The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancerYidong Ge0Lili Kong1Yuxuan Li2Zongdong Yu3Fengguang Zhai4Ziqing Zhan5Gun Chen6Shuyan Wang7Haoyun Wang8Yuxuan Wang9Jianan Zhao10Lechen Hu11Jianing Mao12Siyuan Wang13Jiaxin Shi14Mengxiang Zhao15Pengrong Lou16Meng Ye17Xiaofeng Jin18Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Neurosurgery, Shangrao People’s HospitalDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityThe Affiliated people’s Hospital of Ningbo UniversityDepartment of Histopathology, Ningbo Clinical Pathology Diagnosis CenterDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityDepartment of Biochemistry and Molecular Biology, Health Science Center, Ningbo UniversityAbstract Paclitaxel combination therapy is the main chemotherapy regimen for endometrial cancer (EC); however, subsequent drug resistance is a bottleneck limiting its widespread clinical application. We found that human insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was abnormally elevated in paclitaxel-resistant EC cells and confirmed that the reduction of IGF2BP3 can effectively improve the sensitivity of EC cells to paclitaxel in vitro and in vivo. Mechanistically, elevated IGF2BP3 promotes the half-life of c-Myc by competitively inhibiting Speckle-type POZ protein (SPOP)-mediated ubiquitination and degradation of c-Myc. As a transcription factor, c-Myc can bind to the promoter of IGF2BP3, thus contributing to the increased transcription of IGF2BP3 via positive feedback and forming a signaling loop that ultimately causes the accumulation of c-Myc-induced paclitaxel resistance. Based on these findings, the application of c-Myc inhibitors (10058-F4) combined with paclitaxel helped paclitaxel-resistant EC cells regain paclitaxel sensitivity in vitro and in vivo. Together, we reveal the underlying mechanism of paclitaxel resistance in endometrial cancer cells and provide insights into treatment strategies for paclitaxel-resistant EC patients.https://doi.org/10.1038/s42003-025-08065-0 |
| spellingShingle | Yidong Ge Lili Kong Yuxuan Li Zongdong Yu Fengguang Zhai Ziqing Zhan Gun Chen Shuyan Wang Haoyun Wang Yuxuan Wang Jianan Zhao Lechen Hu Jianing Mao Siyuan Wang Jiaxin Shi Mengxiang Zhao Pengrong Lou Meng Ye Xiaofeng Jin The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancer Communications Biology |
| title | The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancer |
| title_full | The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancer |
| title_fullStr | The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancer |
| title_full_unstemmed | The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancer |
| title_short | The role of IGF2BP3/SPOP/c-Myc loop in paclitaxel resistance of endometrial cancer |
| title_sort | role of igf2bp3 spop c myc loop in paclitaxel resistance of endometrial cancer |
| url | https://doi.org/10.1038/s42003-025-08065-0 |
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