BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM.

BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM.
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BPIFB1 (LPLUNC1) 通过与 VTN 和 VIM 相互作用抑制鼻咽癌的迁移和侵袭

DOI:
10.1038/bjc.2017.385
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发表时间:
2018-01
影响因子:
8.8
通讯作者:
Zeng Z
Zeng Z
中科院分区:
医学1区
文献类型:
--
作者:
Wei F;Wu Y;Tang L;He Y;Shi L;Xiong F;Gong Z;Guo C;Li X;Liao Q;Zhang W;Zhou M;Xiang B;Li X;Li Y;Li G;Xiong W;Zeng Z

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背景:杀菌/渗透性增加倍数家族B成员1(BPIFB 1,以前称为LPLUNC 1)在鼻咽部高表达,在鼻咽癌(NPC)中显著下调,与NPC患者的预后相关。由于转移是NPC相关死亡的主要原因,我们探讨了BPIFB 1在NPC迁移和侵袭中的作用。使用免疫共沉淀分析结合质谱法来鉴定BPIFB 1结合蛋白。此外,蛋白质印迹,免疫荧光和免疫组织化学允许评估的分子机制与BPIFB 1特异性转移抑制通过玻连蛋白(VTN)和波形蛋白(Vim)interactions.Results:我们的研究结果表明,BPIFB 1表达显着抑制鼻咽癌细胞迁移,侵袭和肺转移能力。此外,两种BPIFB 1相互作用蛋白VTN和Vim的鉴定表明,BPIFB 1减少NPC细胞中VTN表达和VTN-整合素αV复合物的形成,导致FAK/Src/ERK信号通路的抑制。此外,BPIFB 1衰减NPC细胞的迁移和侵袭,通过抑制VTN或VIM诱导的上皮间质transition.Conclusions:这项研究代表了第一次证明BPIFB 1在NPC迁移,侵袭和肺转移的功能。我们的研究结果表明,重新表达BPIFB 1可能代表一个有用的策略,预防和治疗鼻咽癌。
Background:Bactericidal/Permeability-increasing-fold-containing family B member 1 (BPIFB1, previously termed LPLUNC1) is highly expressed in the nasopharynx, significantly downregulated in nasopharyngeal carcinoma (NPC), and associated with prognosis in NPC patients. Because metastasis represents the primary cause of NPC-related death, we explored the role of BPIFB1 in NPC migration and invasion.Methods:The role of BPIFB1 in NPC metastasis was investigated in vitro and in vivo. A co-immunoprecipitation assay coupled with mass spectrometry was used to identify BPIFB1-binding proteins. Additionally, western blotting, immunofluorescence, and immunohistochemistry allowed assessment of the molecular mechanisms associated with BPIFB1-specific metastatic inhibition via vitronectin (VTN) and vimentin (VIM) interactions.Results:Our results showed that BPIFB1 expression markedly inhibited NPC cell migration, invasion, and lung-metastatic abilities. Additionally, identification of two BPIFB1-interacting proteins, VTN and VIM, showed that BPIFB1 reduced VTN expression and the formation of a VTN-integrin αV complex in NPC cells, leading to inhibition of the FAK/Src/ERK signalling pathway. Moreover, BPIFB1 attenuated NPC cell migration and invasion by inhibiting VTN-or VIM-induced epithelial–mesenchymal transition.Conclusions:This study represents the first demonstration of BPIFB1 function in NPC migration, invasion, and lung metastasis. Our findings indicate that re-expression of BPIFB1 might represent a useful strategy for preventing and treating NPC.
DOI: 10.1038/srep20500
发表时间: 2016-02-05
期刊: Scientific reports
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期刊: ONCOLOGY REPORTS
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发表时间: 2011-03-29
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