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 and Dario C. Altieri ()
Additional contact information
M. Cecilia Caino: Prostate Cancer Discovery and Development Program, The Wistar Institute
Jae Ho Seo: Prostate Cancer Discovery and Development Program, The Wistar Institute
Angeline Aguinaldo: Drexel University College of Engineering
Eric Wait: Drexel University College of Engineering
Kelly G. Bryant: Prostate Cancer Discovery and Development Program, The Wistar Institute
Andrew V. Kossenkov: Center for Systems and Computational Biology, The Wistar Institute
James E. Hayden: Imaging Shared Resource, The Wistar Institute Cancer Center
Valentina Vaira: Istituto Nazionale Genetica Molecolare ‘Romeo and Enrica Invernizzi’
Annamaria Morotti: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
Stefano Ferrero: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
Silvano Bosari: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
Dmitry I. Gabrilovich: Prostate Cancer Discovery and Development Program, The Wistar Institute
Lucia R. Languino: Prostate Cancer Discovery and Development Program, The Wistar Institute
Andrew R. Cohen: Drexel University College of Engineering
Dario C. Altieri: Prostate Cancer Discovery and Development Program, The Wistar Institute

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13730

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