Document Type
Article
Publication Date
12-19-2016
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.
Recommended Citation
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.; and Altieri, Dario C., "A neuronal network of mitochondrial dynamics regulates metastasis." (2016). Department of Cancer Biology Faculty Papers. Paper 108.
https://jdc.jefferson.edu/cbfp/108
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
27991488
Comments
This article has been peer reviewed. It is the author’s final published version in Nature Communications
Volume 7, December 2016, Article number 13730.
The published version is available at DOI: 10.1038/ncomms13730. Copyright © Caino et al.