A neuronal network of mitochondrial dynamics regulates metastasis

作者：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; Altieri Dario C

来源：Nature Communications, 2016, 7(1): 13730.

DOI：10.1038/ncomms13730

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.

• 出版日期2016-12-19