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

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)

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Caino, M. C., Seo, J. H., Aguinaldo, A., Wait, E., Bryant, K. G., Kossenkov, A. V., Hayden, J. E., Vaira, V., Morotti, A., Ferrero, S., Bosari, S., Gabrilovich, D. I., Languino, L. R., Cohen, A. R., & Altieri, D. C. (2016). A neuronal network of mitochondrial dynamics regulates metastasis. Nature Communications, 7, [13730]. https://doi.org/10.1038/ncomms13730

A neuronal network of mitochondrial dynamics regulates metastasis. / Caino, M. Cecilia; Seo, Jae Ho; Aguinaldo, Angeline; Wait, Eric; Bryant, Kelly G.; Kossenkov, Andrew V.; Hayden, James E.; Vaira, Valentina; Morotti, Annamaria; Ferrero, Stefano; Bosari, Silvano; Gabrilovich, Dmitry I.; Languino, Lucia R.; Cohen, Andrew R.; Altieri, Dario C.

In: Nature Communications, Vol. 7, 13730, 19.12.2016.

Research output: Contribution to journal › Article

Caino, M. Cecilia ; Seo, Jae Ho ; Aguinaldo, Angeline ; Wait, Eric ; Bryant, Kelly G. ; Kossenkov, Andrew V. ; Hayden, James E. ; Vaira, Valentina ; Morotti, Annamaria ; Ferrero, Stefano ; Bosari, Silvano ; Gabrilovich, Dmitry I. ; Languino, Lucia R. ; Cohen, Andrew R. ; Altieri, Dario C. / A neuronal network of mitochondrial dynamics regulates metastasis. In: Nature Communications. 2016 ; Vol. 7.

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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.",

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AU - Hayden, James E.

AU - Vaira, Valentina

AU - Morotti, Annamaria

AU - Ferrero, Stefano

AU - Bosari, Silvano

AU - Gabrilovich, Dmitry I.

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AU - Cohen, Andrew R.

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