Resistin facilitates breast cancer progression via TLR4- mediated induction of mesenchymal phenotypes and stemness properties

C. H. Wang, P. J. Wang, Y. C. Hsieh, S. Lo, Y. C. Lee, Y. C. Chen, C. H. Tsai, W. C. Chiu, S. Chu Sung Hu, C. W. Lu, Y. F. Yang, C. C. Chiu, F. Ou-Yang, Y. M. Wang, M. F. Hou, S. S.F. Yuan

研究成果: 雜誌貢獻文章

28 引文 斯高帕斯(Scopus)

摘要

Growing evidence indicates that resistin - an obesity-related cytokine - is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells - mechanisms critical to tumorigenesis and metastasis - through a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4-specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-κB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer.
原文英語
頁(從 - 到)589-600
頁數12
期刊Oncogene
37
發行號5
DOIs
出版狀態已發佈 - 二月 1 2018
對外發佈Yes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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