A neuronal network of mitochondrial dynamics regulates metastasis

M. Cecilia Caino; Jae Ho Seo; Angeline Aguinaldo; Eric Wait; Kelly G. Bryant; Andrew V. Kossenkov; James E. Hayden; Valentina Vaira; Annamaria Morotti; Stefano Ferrero; Silvano Bosari; Dmitry I. Gabrilovich; Lucia R. Languino; Andrew R. Cohen; Dario C. Altieri

doi:10.1038/ncomms13730

A neuronal network of mitochondrial dynamics regulates metastasis

M. Cecilia Caino, Jae Ho Seo, Angeline Aguinaldo, Eric Wait, Kelly G. Bryant, Andrew V. Kossenkov, James E. Hayden, Valentina Vaira, Annamaria Morotti, Stefano Ferrero, Silvano Bosari, Dmitry I. Gabrilovich, Lucia R. Languino, Andrew R. Cohen, Dario C. Altieri

Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	13730
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13730
Publication status	Published - Dec 19 2016

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

Access to Document

10.1038/ncomms13730

Cite this

@article{26dc7a971502453da6e77b4219f2f21f,

title = "A neuronal network of mitochondrial dynamics regulates metastasis",

abstract = "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.",

author = "Caino, {M. Cecilia} and Seo, {Jae Ho} and Angeline Aguinaldo and Eric Wait and Bryant, {Kelly G.} and Kossenkov, {Andrew V.} and Hayden, {James E.} and Valentina Vaira and Annamaria Morotti and Stefano Ferrero and Silvano Bosari and Gabrilovich, {Dmitry I.} and Languino, {Lucia R.} and Cohen, {Andrew R.} and Altieri, {Dario C.}",

year = "2016",

month = dec,

day = "19",

doi = "10.1038/ncomms13730",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "NLM (Medline)",

}

TY - JOUR

T1 - A neuronal network of mitochondrial dynamics regulates metastasis

AU - Caino, M. Cecilia

AU - Seo, Jae Ho

AU - Aguinaldo, Angeline

AU - Wait, Eric

AU - Bryant, Kelly G.

AU - Kossenkov, Andrew V.

AU - Hayden, James E.

AU - Vaira, Valentina

AU - Morotti, Annamaria

AU - Ferrero, Stefano

AU - Bosari, Silvano

AU - Gabrilovich, Dmitry I.

AU - Languino, Lucia R.

AU - Cohen, Andrew R.

AU - Altieri, Dario C.

PY - 2016/12/19

Y1 - 2016/12/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85006835178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006835178&partnerID=8YFLogxK

U2 - 10.1038/ncomms13730

DO - 10.1038/ncomms13730

M3 - Article

AN - SCOPUS:85006835178

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 13730

ER -

A neuronal network of mitochondrial dynamics regulates metastasis

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this