A Neuronal Network of Mitochondrial Dynamics Regulates Metastasis

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Dec 20

PMID 27991488

Citations 78

Authors

M Cecilia Caino

Jae Ho Seo

Angeline Aguinaldo

Eric Wait

Kelly G Bryant

Andrew V Kossenkov

James E Hayden

Valentina Vaira

Annamaria Morotti

Stefano Ferrero

Silvano Bosari

Dmitry I Gabrilovich

Lucia R Languino

Andrew R Cohen

Dario C Altieri

Affiliations

Soon will be listed here.

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.

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