A neuronal network of mitochondrial dynamics regulates metastasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27991488.
- Also identified by DOI 10.1038/ncomms13730 and PMC identifier 5187409.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Kinesins
- Mitochondrial Dynamics
- Mitochondrial Proteins
- Neoplasm Metastasis
- Nerve Tissue Proteins
- Vesicular Transport Proteins
- rho GTP-Binding Proteins