Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer
Abstract Breast cancer (BC) is the most prevalent and highly heterogeneous malignancy affecting females worldwide, and its development is closely linked to metabolic reprogramming. In this study, label-free quantification (LFQ) was used to analyze the protein expression in exosomes secreted by BC dr...
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2025-07-01
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| Series: | Cellular and Molecular Life Sciences |
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| Online Access: | https://doi.org/10.1007/s00018-025-05788-5 |
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| author | Yuxin Ji Ruonan Li Guohui Tang Yuhan Xiao Ruyin Ye Jiwen Shi Chenchen Geng Ruorong Ran Chengle Zhu Wenrui Wang Changjie Chen Qingling Yang |
| author_facet | Yuxin Ji Ruonan Li Guohui Tang Yuhan Xiao Ruyin Ye Jiwen Shi Chenchen Geng Ruorong Ran Chengle Zhu Wenrui Wang Changjie Chen Qingling Yang |
| author_sort | Yuxin Ji |
| collection | DOAJ |
| description | Abstract Breast cancer (BC) is the most prevalent and highly heterogeneous malignancy affecting females worldwide, and its development is closely linked to metabolic reprogramming. In this study, label-free quantification (LFQ) was used to analyze the protein expression in exosomes secreted by BC drug-resistant cells, identifying RAS-associated binding protein (RAB) 10 as the most significantly upregulated protein. RAB10, a member of the small GTPase family with complex biological functions, is highly expressed in BC and is associated with poor prognosis. In this study, we mainly utilized mouse breast cancer 4T-1 cells (wild-type control cells) and tumor-induced 4T-1 cells (isolated from mouse in situ tumor tissues to simulate the phenotype of the in vivo tumor microenvironment), and on this basis, conducted in vitro functional verification and in vivo tumorigenesis experiments. A comprehensive multi-omics analysis, including metabolomics and proteomics, following RAB10 knockdown, demonstrated the crucial role of RAB10 in regulating central carbon metabolism, which is essential for autophagy and ferroptosis in BC cells. Our study further confirmed that RAB10 mediates metabolic reprogramming in BC cells by regulating the Slc37a2/mTOR pathway, leading to enhanced autophagy and inhibition of ferroptosis. This comprehensive multi-omics analysis elucidated the key molecular and regulatory mechanisms underlying RAB10-induced metabolic reprogramming in tumors, providing potential new therapeutic targets and biomarkers for prognostic assessment in BC treatment. |
| format | Article |
| id | doaj-art-68b12b8632694348963ffe0e4b0c2e5a |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-68b12b8632694348963ffe0e4b0c2e5a2025-08-20T04:01:53ZengSpringerCellular and Molecular Life Sciences1420-90712025-07-0182112410.1007/s00018-025-05788-5Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancerYuxin Ji0Ruonan Li1Guohui Tang2Yuhan Xiao3Ruyin Ye4Jiwen Shi5Chenchen Geng6Ruorong Ran7Chengle Zhu8Wenrui Wang9Changjie Chen10Qingling Yang11Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityAnhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical UniversityDepartment of Life Sciences, Bengbu Medical UniversityDepartment of Biochemistry and Molecular Biology, Bengbu Medical UniversityDepartment of Biochemistry and Molecular Biology, Bengbu Medical UniversityAbstract Breast cancer (BC) is the most prevalent and highly heterogeneous malignancy affecting females worldwide, and its development is closely linked to metabolic reprogramming. In this study, label-free quantification (LFQ) was used to analyze the protein expression in exosomes secreted by BC drug-resistant cells, identifying RAS-associated binding protein (RAB) 10 as the most significantly upregulated protein. RAB10, a member of the small GTPase family with complex biological functions, is highly expressed in BC and is associated with poor prognosis. In this study, we mainly utilized mouse breast cancer 4T-1 cells (wild-type control cells) and tumor-induced 4T-1 cells (isolated from mouse in situ tumor tissues to simulate the phenotype of the in vivo tumor microenvironment), and on this basis, conducted in vitro functional verification and in vivo tumorigenesis experiments. A comprehensive multi-omics analysis, including metabolomics and proteomics, following RAB10 knockdown, demonstrated the crucial role of RAB10 in regulating central carbon metabolism, which is essential for autophagy and ferroptosis in BC cells. Our study further confirmed that RAB10 mediates metabolic reprogramming in BC cells by regulating the Slc37a2/mTOR pathway, leading to enhanced autophagy and inhibition of ferroptosis. This comprehensive multi-omics analysis elucidated the key molecular and regulatory mechanisms underlying RAB10-induced metabolic reprogramming in tumors, providing potential new therapeutic targets and biomarkers for prognostic assessment in BC treatment.https://doi.org/10.1007/s00018-025-05788-5Breast cancerRAB10MetabolismAutophagyFerroptosis |
| spellingShingle | Yuxin Ji Ruonan Li Guohui Tang Yuhan Xiao Ruyin Ye Jiwen Shi Chenchen Geng Ruorong Ran Chengle Zhu Wenrui Wang Changjie Chen Qingling Yang Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer Cellular and Molecular Life Sciences Breast cancer RAB10 Metabolism Autophagy Ferroptosis |
| title | Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer |
| title_full | Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer |
| title_fullStr | Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer |
| title_full_unstemmed | Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer |
| title_short | Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer |
| title_sort | integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by rab10 through slc37a2 mtor pathway in breast cancer |
| topic | Breast cancer RAB10 Metabolism Autophagy Ferroptosis |
| url | https://doi.org/10.1007/s00018-025-05788-5 |
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