TY - JOUR
T1 - A neuronal network of mitochondrial dynamics regulates metastasis
AU - Caino, M. Cecilia
AU - Seo, Jae Ho
AU - Aguinaldo, Angeline
AU - Wait, Eric
AU - Bryant, Kelly G.
AU - Kossenkov, Andrew V.
AU - Hayden, James E.
AU - Vaira, Valentina
AU - Morotti, Annamaria
AU - Ferrero, Stefano
AU - Bosari, Silvano
AU - Gabrilovich, Dmitry I.
AU - Languino, Lucia R.
AU - Cohen, Andrew R.
AU - Altieri, Dario C.
PY - 2016/12/19
Y1 - 2016/12/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85006835178&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006835178&partnerID=8YFLogxK
U2 - 10.1038/ncomms13730
DO - 10.1038/ncomms13730
M3 - Article
AN - SCOPUS:85006835178
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 13730
ER -