title: Toll-like receptor 2 mediates invasion via activating NF-kappaB in MDA-MB-231 breast cancer cells.
abstract: MDA-MB-231 breast cancer cells have a high invasive potential, yet the mechanisms involved are not known. This study showed that Toll-like receptor 2 (TLR2) was highly expressed in MDA-MB-231 cells and played a critical role in cell invasion. Compared with the poorly invasive MCF-7 cells, MDA-MB-231 cells expressed 10.5-fold more TLR2. Using TLR2 agonist pg-LPS and TLR2 neutralizing antibody, we found that TLR2 activation significantly promoted MDA-MB-231 invasion, whereas TLR2 blockade diminished this capacity. TLR2 activation enhanced the activity of NF-kappaB and induced phosphorylation of TAK1 and IkappaBalpha in the TLR2/NF-kappaB signaling pathway in MDA-MB-231, but not in MCF-7 cells. TLR2 activation increased IL-6, TGF-beta, VEGF and MMP9 secretion, which are associated with TLR2-NF-kappaB signaling. We demonstrated that TLR2 is a critical receptor responsible for NF-kappaB signaling activity and highly invasive capacity of MDA-MB-231 cells.
authors.affiliation: Molecular Immunology and Pharmacology Laboratory, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan St., Beijing 100050, China. xiewj75@126.com
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xie
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yafang
authors.initials: Y
authors.lastname: Huang
authors.forename: Hongzhen
authors.initials: H
authors.lastname: Yang
authors.forename: Jiaping
authors.initials: J
authors.lastname: Wang
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Hu
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9