A neuronal network of mitochondrial dynamics regulates metastasis

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M Cecilia Caino1,2, Jae Ho Seo1,2, Angeline Aguinaldo3

  • 1Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

Nature Communications
|December 20, 2016
PubMed

Insights

Mitochondria

Area of Science:

  • Cell Biology
  • Cancer Research
  • Mitochondrial Dynamics

Background:

  • The role of mitochondria in cancer progression remains debated.
  • Mitochondrial localization and dynamics are crucial for cellular functions, including migration.

Purpose of the Study:

  • To investigate the role of mitochondrial dynamics in cancer metastasis.
  • To identify key regulators of mitochondrial trafficking in tumor cells.

Main Methods:

  • Genome-wide shRNA screening in tumor models.
  • Analysis of mitochondrial dynamics and localization using live-cell imaging.
  • Correlation of protein expression with patient survival and clinical data.

Main Results:

  • Tumors reprogram a neuronal mitochondrial network, including syntaphilin (SNPH), kinesin KIF5B, and Miro1/2, to traffic mitochondria to the cell cortex.
  • SNPH expression suppresses mitochondrial movement, organelle dynamics, and blocks tumor cell chemotaxis and metastasis in vivo.
  • Downregulation or loss of SNPH in human tumors correlates with shorter patient survival, increased cortical mitochondrial trafficking, and heightened cell invasion.

Conclusions:

  • A syntaphilin (SNPH) regulatory network controls mitochondrial localization and dynamics, impacting cancer cell metastatic potential.
  • SNPH acts as a suppressor of metastasis by regulating mitochondrial trafficking.
  • The SNPH network represents a potential therapeutic target for inhibiting cancer metastasis.

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