title: Metadherin mediates lipopolysaccharide-induced migration and invasion of breast cancer cells.
abstract: BACKGROUND
  Breast cancer is the most prevalent cancer in women worldwide and metastatic breast cancer has very poor prognosis. Inflammation has been implicated in migration and metastasis of breast cancer, although the exact molecular mechanism remains elusive.
  
  
  RESULTS
  We show that the pro-inflammatory endotoxin Lipopolysaccharide (LPS) upregulates the expression of Metadherin (MTDH), a recently identified oncogene, in a number of breast cancer lines. Stable knockdown of MTDH by shRNA in human breast MDA-MB-231 cells abolishes LPS-induced cell migration and invasion as determined by several in vitro assays. In addition, knockdown of MTDH diminishes Nuclear Factor-kappa B (NF-κB) activation by LPS and inhibited LPS-induced IL-8 and MMP-9 production.
  
  
  CONCLUSIONS
  These results strongly suggest that MTDH is a pivotal molecule in inflammation-mediated tumor metastasis. Since NF-κB, IL-8 and MMP-9 play roles in LPS-induced invasion or metastasis, the mechanism of MTDH-promoted invasion and metastasis may be through the activation of NF-κB, IL-8 and MMP-9, also suggesting a role of MTDH in regulating both inflammatory responses and inflammation-associated tumor invasion. These findings indicate that MTDH is involved in inflammation-induced tumor progression, and support that MTDH targeting therapy may hold promising prospects in treating breast cancer.
authors.affiliation: Department of Breast Surgery, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Kong
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
authors.forename: Cunzhong
authors.initials: C
authors.lastname: Yuan
authors.forename: Wenwei
authors.initials: W
authors.lastname: Hu
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D001681:Biological Assay; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D059016:Tumor Microenvironment; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D008070:Lipopolysaccharides; C483039:MTDH protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4