title: Triggering of Toll-like receptor 4 on metastatic breast cancer cells promotes αvβ3-mediated adhesion and invasive migration.
abstract: Triggering of Toll-like receptor 4 (TLR4) on tumor cells has been found to promote tumor progression by promoting tumor cell proliferation and survival. So far, however, the effect of TLR4 signaling on tumor metastasis has not been well elucidated. Here, we report that triggering of TLR4 on metastatic breast cancer cells could reciprocally regulate the expression of αvβ3 and the expressions of TPM1 and maspin, and promote αvβ3-mediated adhesion and invasive migration of the cells. In metastatic breast cancer cells, TLR4 signaling increased the expression of integrin αvβ3 by activating NF-κB, resulting in the increased adhesion capacity of tumor cells to the ligand for αvβ3, and the increased polymerization of actin and production of MMP-9 in tumor cells in response to ECM. HoxD3 was required for the up-regulation of αv and β3 expressions by NF-κB. Moreover, TLR4 signaling increased the expression of miR-21 in breast cancer cells by activating NF-κB. Accordingly, the expressions of TPM1 and maspin were decreased at protein level, whereas the transcription activity of these genes was not influenced. Consistent with the promoting effect on αvβ3-mediated adhesion and invasive migration, TLR4 signaling promoted the arrest of metastatic breast cancer cells in circulation and following invasion. The effect of TLR4 signaling could be abrogated by inhibiting NF-κB. These findings suggest that metastatic breast cancer cells could acquire higher metastatic potential due to triggering of TLR4 and activation of NF-κB in the cells, and that both TLR4 and NF-κB could be therapeutic targets for preventing metastasis of breast cancer cells.
authors: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, The People's Republic of China.
authors: Sheng-Jun
authors: SJ
authors: Liao
authors: Yuan-Hong
authors: YH
authors: Zhou
authors: Ye
authors: Y
authors: Yuan
authors: Dong
authors: D
authors: Li
authors: Feng-Hua
authors: FH
authors: Wu
authors: Qi
authors: Q
authors: Wang
authors: Jian-Hua
authors: JH
authors: Zhu
authors: Bin
authors: B
authors: Yan
authors: Jing-Jing
authors: JJ
authors: Wei
authors: Gui-Mei
authors: GM
authors: Zhang
authors: Zuo-Hua
authors: ZH
authors: Feng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009362:Neoplasm Metastasis; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015843:Serpins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014335:Tropomyosin / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D039302:Integrin alphaVbeta3; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C085344:SERPIN-B5; D015843:Serpins; C490775:TPM1 protein, human; D051197:Toll-Like Receptor 4; D014157:Transcription Factors; D014335:Tropomyosin; C073547:HOXA4 protein, human