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Nat Commun. 2016 Dec 19;7:13730. doi: 10.1038/ncomms13730.

A neuronal network of mitochondrial dynamics regulates metastasis.

Author information

1
Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
2
Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
3
Department of Electrical and Computer Engineering, Drexel University College of Engineering, Philadelphia, Pennsylvania 19104, USA.
4
Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
5
Imaging Shared Resource, The Wistar Institute Cancer Center, Philadelphia, Pennsylvania 19104, USA.
6
Istituto Nazionale Genetica Molecolare 'Romeo and Enrica Invernizzi', Milan 20122, Italy.
7
Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
8
Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy.
9
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan 20122, Italy.
10
Translational Tumor Immunology Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
11
Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

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.

PMID:
27991488
PMCID:
PMC5187409
DOI:
10.1038/ncomms13730
[Indexed for MEDLINE]
Free PMC Article

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