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.

A neuronal network of mitochondrial dynamics regulates metastasis / M.C. Caino, J. Seo, A. Aguinaldo, E. Wait, K. Bryant, A. Kossenkov, J. Hayden, V. Vaira, A. Morotti, S. Ferrero, S. Bosari, D. Gabrilovich, L. Languino, A. Cohen, D. Altieri. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 7(2016 Dec 19), pp. 13730.1-13730.11. [10.1038/ncomms13730]

A neuronal network of mitochondrial dynamics regulates metastasis

V. Vaira
;
A. Morotti
;
S. Ferrero;S. Bosari
;
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.
Settore MED/08 - Anatomia Patologica
Settore BIO/11 - Biologia Molecolare
19-dic-2016
Article (author)
File in questo prodotto:
File Dimensione Formato  
ncomms13730.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 2.14 MB
Formato Adobe PDF
2.14 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/467777
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 84
  • ???jsp.display-item.citation.isi??? 85
social impact