Atg5 Disassociates the V1V0-ATPase to Promote Exosome Production and Tumor Metastasis Independent of Canonical Macroautophagy

被引：224

作者：

Guo, Huishan ^{[1
]}

Chitiprolu, Maneka ^{[1
]}

Roncevic, Luc ^{[1
]}

Javalet, Charlotte ^{[3
,4
]}

Hemming, Fiona J. ^{[3
,4
]}

Trung, My Tran ^{[1
]}

Meng, Lingrui ^{[1
]}

Latreille, Elyse ^{[1
]}

de Souza, Christiano Tanese ^{[5
]}

McCulloch, Danielle ^{[1
]}

Baldwin, R. Mitchell ^{[1
]}

Auer, Rebecca ^{[5
]}

Cote, Jocelyn ^{[1
]}

Russell, Ryan Charles ^{[1
]}

Sadoul, Remy ^{[3
,4
]}

Gibbings, Derrick ^{[1
,2
]}

机构：

[1] Univ Ottawa, Dept Cellular & Mol Med, 3131 Roger Guindon Hall,451 Smyth Rd, Ottawa, ON K1H 8M5, Canada

[2] Univ Ottawa, Ottawa Inst Syst Biol, Ottawa, ON K1H 8M5, Canada

[3] INSERM, U1216, F-38042 Grenoble, France

[4] Univ Grenoble Alpes, Inst Neurosci, F-38042 Grenoble, France

[5] Ottawa Hosp Res Inst, Ottawa, ON K1H 8L6, Canada

来源：

DEVELOPMENTAL CELL | 2017年 / 43卷 / 06期

基金：

加拿大健康研究院;

关键词：

EXTRACELLULAR VESICLES; MULTIVESICULAR ENDOSOMES; AUTOPHAGY PROTEINS; ESCRT MACHINERY; PATHWAY; BIOGENESIS; MATURATION; SECRETION; CELLS; ACIDIFICATION;

D O I：

10.1016/j.devcel.2017.11.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Autophagy and autophagy-related genes (Atg) have been attributed prominent roles in tumorigenesis, tumor growth, and metastasis. Extracellular vesicles called exosomes are also implicated in cancer metastasis. Here, we demonstrate that exosome production is strongly reduced in cells lacking Atg5 and Atg16L1, but this is independent of Atg7 and canonical autophagy. Atg5 specifically decreases acidification of late endosomes where exosomes are produced, disrupting the acidifying V1V0-ATPase by removing a regulatory component, ATP6V1E1, into exosomes. The effect of Atg5 on exosome production promotes the migration and in vivo metastasis of orthotopic breast cancer cells. These findings uncover mechanisms controlling exosome release and identify means by which autophagy-related genes can contribute to metastasis in autophagy-independent pathways.

引用

页码：716 / +

页数：22

共 63 条

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