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学科主题: 临床医学
题名:
Unconventional secretion of synuclein-gamma promotes tumor cell invasion
作者: Liu, Caiyun1; Qu, Like1; Lian, Shenyi1; Tian, Zhihua2; Zhao, Chuanke1; Meng, Lin1; Shou, Chengchao1
关键词: invasion ; phosphatidylinositide 3-kinase (PI3K) ; synuclein- (SNCG) ; unconventional secretion ; vesicle-associated protein
刊名: FEBS JOURNAL
发表日期: 2014-11-01
DOI: 10.1111/febs.13055
卷: 281, 期:22, 页:5159-5171
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: GROWTH-FACTOR 2 ; BREAST-CANCER ; ALPHA-SYNUCLEIN ; PHOSPHATIDYLINOSITOL 3-KINASE ; MEMBRANE TRAFFICKING ; MAMMALIAN-CELLS ; EXOSOME RELEASE ; PLASMA-MEMBRANE ; COLON-CANCER ; PROTEIN
英文摘要:

Synuclein- (SNCG) is a chaperone protein and exists mainly in the cytoplasm. SNCG confers chemoresistance, and is a potential unfavorable biomarker for multiple types of cancer. Our previous work demonstrated that SNCG could be detected in the serum of cancer patients and the medium of cultured cancer cells, but the mechanism of SNCG secretion and its biological roles are unknown. Here, we showed that SNCG levels in the culture medium were positively correlated with cancer cell densities and the concentrations of fetal bovine serum added. SNCG secretion was unaffected by brefeldin A, an inhibitor of the classic protein transport pathway, but was antagonized by exosome inhibitor, lysosome inhibitor, ABC transporter inhibitor, and phosphatidylinositide 3-kinase inhibitor, and knockdown of Rab27a. Ultracentrifugation fractionation revealed that intracellular SNCG was present as both free and vesicle-associated forms, but that the extracellular SNCG was mainly free. The results of reciprocal coimmunoprecipitation experiments showed an interaction between SNCG and flotillin-2, a marker of exosomes and lipid rafts. Moreover, we demonstrated that SNCG, both secreted from tumor cells and exogenously added, markedly promoted cancer cell migration and invasion, but had no effect on noncancerous cells. These findings suggest that SNCG is actively secreted by cancer cells via an unconventional secretion pathway and contributes to aggressive phenotypes of cancer cells.

Structured digital abstract center dot withby(,).

语种: 英语
所属项目编号: 81272410 ; 2010CB529303
项目资助者: National Natural Science Foundation of China ; National 973 Program
WOS记录号: WOS:000344795900016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57331
Appears in Collections:北京大学临床肿瘤学院_中心实验室_期刊论文

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作者单位: 1.Peking Univ, Canc Hosp & Inst, Dept Biochem & Mol Biol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China
2.Peking Univ, Canc Hosp & Inst, Cent Lab, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China

Recommended Citation:
Liu, Caiyun,Qu, Like,Lian, Shenyi,et al. Unconventional secretion of synuclein-gamma promotes tumor cell invasion[J]. FEBS JOURNAL,2014,281(22):5159-5171.
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