Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月14日

查看全文
  • Yuxin Ji,
  • Ruonan Li,
  • Guohui Tang,
  • Yuhan Xiao,
  • Ruyin Ye,
  • Jiwen Shi,
  • Chenchen Geng,
  • Ruorong Ran,
  • Chengle Zhu,
  • Wenrui Wang,
  • Changjie Chen,
  • Qingling Yang

摘要

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.