title: TRAIL suppresses human breast cancer cell migration via MADD/CXCR7.
abstract: BACKGROUND
  Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can specifically induce apoptosis limited to various cancer cells, so this reagent is considered a promising medicine for cancer therapy. TRAIL also exerts effects on non-apoptotic signals, relevant to processes such as metastasis, autophagy and proliferation in cancer cells. However, the mechanisms of TRAIL-regulated non-apoptotic signals are unclear. The purpose of this study was to investigate MADD/CXCR7 effects in TRAIL-mediated breast cancer cell migration.
  
  
  METHODS
  The ability of MADD/CXCR7 to regulate MVP signaling in TRAIL-mediated breast cancer cells migration was evaluated by transwell migration assay, quantitative RT-PCR, Western blotting and knock down experiments.
  
  
  RESULTS
  In this study, we found that treatment with TRAIL resulted in induced expression levels of MADD and CXCR7 in breast cancer cells. Knock down of MADD followed by treatment with TRAIL resulted in increased cell migration compared to either treatment alone. Similarly, through overexpression and knockdown experiments, we demonstrated that CXCR7 also positively regulated TRAIL- inhibited migration. Surprisingly, knock down of MADD lead to inhibition of TRAIL-induced CXCR7 mRNA and protein expression and overexpression of CXCR7 lead to the reduction of MADD expression, indicating that MADD is an upstream regulatory factor of TRAIL-triggered CXCR7 production and a negative feedback mechanism between MADD and CXCR7. Furthermore, we showed that CXCR7 is involved in MADD-inhibited migration in breast cancer cells.
  
  
  CONCLUSIONS
  Our work defined a novel signaling pathway implicated in the control of breast cancer migration.
authors: Department of Breast and Thyroid Sugery, The First Affiliated Hospital of Liaoning Medical University. Jinzhou, Liaoning, China E-mail : wangr0428@163.com, lijcwr@163.com.
authors: Rui
authors: R
authors: Wang
authors: Jin-Cheng
authors: JC
authors: Li
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C501896:ACKR3 protein, human; D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; C105852:MADD protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human