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A neuronal network of mitochondrial dynamics regulates metastasis

Author

Listed:
  • M. Cecilia Caino

    (Prostate Cancer Discovery and Development Program, The Wistar Institute
    Tumor Microenvironment and Metastasis Program, The Wistar Institute)

  • Jae Ho Seo

    (Prostate Cancer Discovery and Development Program, The Wistar Institute
    Tumor Microenvironment and Metastasis 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
    Tumor Microenvironment and Metastasis 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’
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    University of Milan)

  • Annamaria Morotti

    (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    University of Milan)

  • Stefano Ferrero

    (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    Surgical and Dental Sciences, University of Milan)

  • Silvano Bosari

    (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
    University of Milan)

  • Dmitry I. Gabrilovich

    (Prostate Cancer Discovery and Development Program, The Wistar Institute
    Translational Tumor Immunology Program, The Wistar Institute)

  • Lucia R. Languino

    (Prostate Cancer Discovery and Development Program, The Wistar Institute
    Thomas Jefferson University)

  • Andrew R. Cohen

    (Drexel University College of Engineering)

  • Dario C. Altieri

    (Prostate Cancer Discovery and Development Program, The Wistar Institute
    Tumor Microenvironment and Metastasis Program, The Wistar Institute)

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.

Suggested Citation

  • 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 & Dmit, 2016. "A neuronal network of mitochondrial dynamics regulates metastasis," Nature Communications, Nature, vol. 7(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13730
    DOI: 10.1038/ncomms13730
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