Breast cancer metastasis suppressor 1 inhibits SDF-1alpha-induced migration of non-small cell lung cancer by decreasing CXCR4 expression.
This report shows that over-expression of BRMS1 reduces SDF-induced chemotaxis and suppresses nuclear factor-kappaB (NF-kappaB) activity in NSCLC cell line. Inhibition of NF-kappaB activity impairs SDF-1alpha-dependent migration and NF-kappaB can directly bind to the chemokine (C-X-C motif) receptor 4 (CXCR4) promoter invivo. However, knockdown of BRMS1 promotes NSCLC cell migration and CXCR4 expression. Furthermore, BRMS1 and CXCR4 expression levels are inversely correlated in the NSCLC cases. The level of BRMS1 mRNA is found to be markedly lower in the distant metastasis group than in the non-distant metastasis group (P=0.003). However, CXCR4 mRNA was higher in the distant metastasis group than in the non-distant metastasis group (P=0.032). These results indicate that BRMS1 regulates metastatic potential at least in part through the down-regulation of CXCR4, to be indirectly regulated by BRMS1 through nuclear factor-kappaB activation.
Yang
Jiyun
J
The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Medical Science Academy and Sichuan Provincial People's Hospital, Sichuan 610071, PR China. yangjiyun@yeah.net
Zhang
Ben
B
Lin
Yin
Y
Yang
Yang
Y
Liu
Xiaoqi
X
Lu
Fang
F
D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors* / Q000502:physiology; D002633:Chemotaxis; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis / Q000037:antagonists & inhibitors*; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
C410024:BRMS1 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha