Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells

Journal of Biomedical Science

Shui-Yi Tung⁸  Hsing-Chun Kuo¹  Cheng-Nan Chen⁶  Yung-Wei Chiu⁵  Tseng-Hsi Lin⁴  Te-Sheng Chang³  Hong-Ren Yu²  Meng Chiao Hsieh⁷  Yi-Hung Kuo⁷  Chih-Chien Chin⁷  Wen-Shih Huang⁷  Chien-Heng Shen³  Yung-Yu Hsieh⁸ 

[1] Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan;Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Insititute of Clinical Medical Science, Chang Gung University College of Medicine, Taoyuan, Taiwan;Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan;Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan;Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan;Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan;Chang Gung University College of Medicine, Taoyuan, Taiwan

关键词: Resistin;    NF-κB;    TLR4;    Obesity;    Gastric cancer;   

Others  :  817333
DOI  :  10.1186/1423-0127-21-59

 received in 2014-03-04, accepted in 2014-05-22,  发布年份 2014

【 摘 要 】

Background

Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells.

Results

Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity.

Conclusions

Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer.

【 授权许可】

   
2014 Hsieh et al.; licensee BioMed Central Ltd.

【 图 表 】

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