PUBLICATION
Resistin facilitates breast cancer progression via TLR4-mediated induction of mesenchymal phenotypes and stemness properties
- 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., Yuan, S.S.
- ID
- ZDB-PUB-181013-10
- Date
- 2018
- Source
- Oncogene 37: 589-600 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Breast/pathology
- Breast Neoplasms/blood
- Breast Neoplasms/pathology*
- Carcinogenesis/pathology
- Cell Line, Tumor
- Disease Progression
- Epithelial-Mesenchymal Transition*
- Female
- Humans
- Lymphatic Metastasis
- Middle Aged
- NF-kappa B
- Neoplasm Staging
- Neoplastic Stem Cells/pathology*
- Resistin/blood
- Resistin/metabolism*
- STAT3 Transcription Factor/metabolism
- Signal Transduction
- Toll-Like Receptor 4/metabolism*
- Up-Regulation
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 28991224 Full text @ Oncogene
Citation
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., Yuan, S.S. (2018) Resistin facilitates breast cancer progression via TLR4-mediated induction of mesenchymal phenotypes and stemness properties. Oncogene. 37:589-600.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping