A neuronal network of mitochondrial dynamics regulates metastasis

被引：106

作者：

Caino, M. Cecilia ^{[1
,2
]}

Seo, Jae Ho ^{[1
,2
]}

Aguinaldo, Angeline ^{[3
]}

Wait, Eric ^{[3
]}

Bryant, Kelly G. ^{[1
,2
]}

Kossenkov, Andrew V. ^{[4
]}

Hayden, James E. ^{[5
]}

Vaira, Valentina ^{[6
,7
,8
]}

Morotti, Annamaria ^{[7
,8
]}

Ferrero, Stefano ^{[7
,9
]}

Bosari, Silvano ^{[7
,8
]}

Gabrilovich, Dmitry I. ^{[1
,10
]}

Languino, Lucia R. ^{[1
,11
,12
]}

Cohen, Andrew R. ^{[3
]}

Altieri, Dario C. ^{[1
,2
]}

机构：

[1] Wistar Inst Anat & Biol, Prostate Canc Discovery & Dev Program, 3601 Spruce St, Philadelphia, PA 19104 USA

[2] Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis Program, 3601 Spruce St, Philadelphia, PA 19104 USA

[3] Drexel Univ, Coll Engn, Dept Elect & Comp Engn, Philadelphia, PA 19104 USA

[4] Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, 3601 Spruce St, Philadelphia, PA 19104 USA

[5] Wistar Inst Anat & Biol, Imaging Shared Resource, 3601 Spruce St, Philadelphia, PA 19104 USA

[6] Ist Nazl Genet Mol Romeo & Enrica Invernizzi, I-20122 Milan, Italy

[7] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Div Pathol, I-20122 Milan, Italy

[8] Univ Milan, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy

[9] Univ Milan, Dept Biomed Surg & Dent Sci, I-20122 Milan, Italy

[10] Wistar Inst Anat & Biol, Translat Tumor Immunol Program, 3601 Spruce St, Philadelphia, PA 19104 USA

[11] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA

[12] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

美国国家卫生研究院;

关键词：

IMAGE-ANALYSIS; BREAST-CANCER; TRAFFICKING; EVOLUTION; MIGRATION; TRACKING; THERAPY; PATHWAY; CELLS;

D O I：

10.1038/ncomms13730

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater membrane dynamics and heightened cell invasion. Therefore, a SNPH network regulates metastatic competence and may provide a therapeutic target in cancer.

引用

页数：11

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