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

Wang, C.-H. et al. (2018) Resistin facilitates breast cancer progression via TLR4-mediated induction of mesenchymal phenotypes and stemness properties. Oncogene, 37, pp. 589-600. (doi: 10.1038/onc.2017.357) (PMID:28991224)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hsieh, Dr Ya-Ching and Lo, Professor Steven
• Authors: Wang, C.-H., Wang, P.-J., Hsieh, Y.-C., Lo, S., Lee, Y.-C., Chen, Y.-C., Tsai, C.-H., Chiu, W.-C., Chu-Sung Hu, S., Lu, C.-W., Yang, Y.-F., Chiu, C.-C., Ou-Yang, F., Wang, Y.-M., Hou, M.-F., and Yuan, S.-S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Oncogene
• Publisher: Nature Publishing Group
• ISSN: 0950-9232
• ISSN (Online): 1476-5594
• Published Online: 09 October 2017
• Copyright Holders: Copyright © 2018 Macmillan Publishers Limited, part of Springer Nature
• First Published: First published in Oncogene 37:589-600
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher