L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer
Abstract The STAT3 pathway promotes epithelial–mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of the key epithelial–mesenchymal transition transcription factor SNAIL in a DNA binding-independent manner. However, the mechanism by which STAT3...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55617-9 |
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| _version_ | 1841559194632716288 |
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| author | Jianpeng Xiao Jie Wang Jialun Li Jie Xiao CuiCui Liu Libi Tan Yanhong Tu Ruifang Yang Yujie Pei Minghua Wang Jiemin Wong Binhua P. Zhou Jing Li Jing Feng |
| author_facet | Jianpeng Xiao Jie Wang Jialun Li Jie Xiao CuiCui Liu Libi Tan Yanhong Tu Ruifang Yang Yujie Pei Minghua Wang Jiemin Wong Binhua P. Zhou Jing Li Jing Feng |
| author_sort | Jianpeng Xiao |
| collection | DOAJ |
| description | Abstract The STAT3 pathway promotes epithelial–mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of the key epithelial–mesenchymal transition transcription factor SNAIL in a DNA binding-independent manner. However, the mechanism by which STAT3 is recruited to the SNAIL promoter to upregulate its expression is still elusive. In our study, the lysine methylation binding protein L3MBTL3 is positively associated with metastasis and poor prognosis in female patients with breast cancer. L3MBTL3 also promotes epithelial–mesenchymal transition and metastasis in breast cancer. Mechanistic analysis reveals that L3MBTL3 interacts with STAT3 and recruits STAT3 to the SNAIL promoter to increase SNAIL transcription levels. The interaction between L3MBTL3 and STAT3 is required for SNAIL transcription upregulation and metastasis in breast cancer, while the methylated lysine binding activity of L3MBTL3 is not required for these functions. In conclusion, L3MBTL3 and STAT3 synergistically upregulate SNAIL expression to promote breast cancer metastasis. |
| format | Article |
| id | doaj-art-1ec7b9ad94664db08539749d4c965256 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1ec7b9ad94664db08539749d4c9652562025-01-05T12:38:53ZengNature PortfolioNature Communications2041-17232025-01-0116112110.1038/s41467-024-55617-9L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancerJianpeng Xiao0Jie Wang1Jialun Li2Jie Xiao3CuiCui Liu4Libi Tan5Yanhong Tu6Ruifang Yang7Yujie Pei8Minghua Wang9Jiemin Wong10Binhua P. Zhou11Jing Li12Jing Feng13The Third School of Clinical Medicine, Southern Medical UniversityThe Third School of Clinical Medicine, Southern Medical UniversityShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal UniversitySchool of Laboratory Medicine and Biotechnology, Southern Medical UniversityDepartment of Laboratory Medicine & Central Laboratory, Southern Medical University Affiliated Fengxian HospitalDepartment of Laboratory Medicine & Central Laboratory, Southern Medical University Affiliated Fengxian HospitalThe Second Affiliated Hospital, The Chinese University of Hong KongAnhui University of Science and Technology Affiliated Fengxian HospitalAnhui University of Science and Technology Affiliated Fengxian HospitalThe Second Affiliated Hospital, The Chinese University of Hong KongShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal UniversityDepartment of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky College of MedicineDepartment of Laboratory Medicine & Central Laboratory, Southern Medical University Affiliated Fengxian HospitalDepartment of Laboratory Medicine & Central Laboratory, Southern Medical University Affiliated Fengxian HospitalAbstract The STAT3 pathway promotes epithelial–mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of the key epithelial–mesenchymal transition transcription factor SNAIL in a DNA binding-independent manner. However, the mechanism by which STAT3 is recruited to the SNAIL promoter to upregulate its expression is still elusive. In our study, the lysine methylation binding protein L3MBTL3 is positively associated with metastasis and poor prognosis in female patients with breast cancer. L3MBTL3 also promotes epithelial–mesenchymal transition and metastasis in breast cancer. Mechanistic analysis reveals that L3MBTL3 interacts with STAT3 and recruits STAT3 to the SNAIL promoter to increase SNAIL transcription levels. The interaction between L3MBTL3 and STAT3 is required for SNAIL transcription upregulation and metastasis in breast cancer, while the methylated lysine binding activity of L3MBTL3 is not required for these functions. In conclusion, L3MBTL3 and STAT3 synergistically upregulate SNAIL expression to promote breast cancer metastasis.https://doi.org/10.1038/s41467-024-55617-9 |
| spellingShingle | Jianpeng Xiao Jie Wang Jialun Li Jie Xiao CuiCui Liu Libi Tan Yanhong Tu Ruifang Yang Yujie Pei Minghua Wang Jiemin Wong Binhua P. Zhou Jing Li Jing Feng L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer Nature Communications |
| title | L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer |
| title_full | L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer |
| title_fullStr | L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer |
| title_full_unstemmed | L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer |
| title_short | L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer |
| title_sort | l3mbtl3 and stat3 collaboratively upregulate snail expression to promote metastasis in female breast cancer |
| url | https://doi.org/10.1038/s41467-024-55617-9 |
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