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

Research output: Contribution to journalArticle

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 languageEnglish
Article number13730
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 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