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

被引：261

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：

071013 [干细胞生物学];

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

收藏

页码：716 / +

页数：22

相关论文

共 63 条

[1]

Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission [J].

Alvarez-Erviti, Lydia ;

Seow, Yiqi ;

Schapira, Anthony H. ;

Gardiner, Chris ;

Sargent, Ian L. ;

Wood, Matthew J. A. ;

Cooper, J. Mark .

NEUROBIOLOGY OF DISEASE, 2011, 42 (03) :360-367

[2]

Syndecan-syntenin-ALIX regulates the biogenesis of exosomes [J].

Baietti, Maria Francesca ;

Zhang, Zhe ;

Mortier, Eva ;

Melchior, Aurelie ;

Degeest, Gisele ;

Geeraerts, Annelies ;

Ivarsson, Ylva ;

Depoortere, Fabienne ;

Coomans, Christien ;

Vermeiren, Elke ;

Zimmermann, Pascale ;

David, Guido .

NATURE CELL BIOLOGY, 2012, 14 (07) :677-685

[3]

Mammalian Autophagy: How Does It Work? [J].

Bento, Carla F. ;

Renna, Maurizio ;

Ghislat, Ghita ;

Puri, Claudia ;

Ashkenazi, Avraham ;

Vicinanza, Mariella ;

Menzies, Fiona M. ;

Rubinsztein, David C. .

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 85, 2016, 85 :685-713

[4]

A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells [J].

Cadwell, Ken ;

Liu, John Y. ;

Brown, Sarah L. ;

Miyoshi, Hiroyuki ;

Loh, Joy ;

Lennerz, Jochen K. ;

Kishi, Chieko ;

Kc, Wumesh ;

Carrero, Javier A. ;

Hunt, Steven ;

Stone, Christian D. ;

Brunt, Elizabeth M. ;

Xavier, Ramnik J. ;

Sleckman, Barry P. ;

Li, Ellen ;

Mizushima, Noboru ;

Stappenbeck, Thaddeus S. ;

Virgin, Herbert W. .

NATURE, 2008, 456 (7219) :259-U62

[5]

Uba1 functions in Atg7-and Atg3-independent autophagy [J].

Chang, Tsun-Kai ;

Shravage, Bhupendra V. ;

Hayes, Sebastian D. ;

Powers, Christine M. ;

Simin, Rachel T. ;

Harper, J. Wade ;

Baehrecke, Eric H. .

NATURE CELL BIOLOGY, 2013, 15 (09) :1067-+

[6]

Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons [J].

Chivet, Mathilde ;

Javalet, Charlotte ;

Laulagnier, Karine ;

Blot, Beatrice ;

Hemming, Fiona J. ;

Sadoul, Remy .

JOURNAL OF EXTRACELLULAR VESICLES, 2014, 3 (01)

[7]

Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles [J].

Colombo, Marina ;

Raposo, Graca ;

Thery, Clotilde .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30, 2014, 30 :255-289

[8]

Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles [J].

Colombo, Marina ;

Moita, Catarina ;

van Niel, Guillaume ;

Kowal, Joanna ;

Vigneron, James ;

Benaroch, Philippe ;

Manel, Nicolas ;

Moita, Luis F. ;

Thery, Clotilde ;

Raposo, Graca .

JOURNAL OF CELL SCIENCE, 2013, 126 (24) :5553-5565

[9]

Recent Insights into the Structure, Regulation, and Function of the V-ATPases [J].

Cotter, Kristina ;

Stransky, Laura ;

McGuire, Christina ;

Forgac, Michael .

TRENDS IN BIOCHEMICAL SCIENCES, 2015, 40 (10) :611-622

[10]

Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes [J].

Florey, Oliver ;

Kim, Sung Eun ;

Sandoval, Cynthia P. ;

Haynes, Cole M. ;

Overholtzer, Michael .

NATURE CELL BIOLOGY, 2011, 13 (11) :1335-U118

← 1 2 3 4 5 6 7 →