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Inhibition of epithelial cell migration and Src/FAK signaling by SIRT3

Jaewon J Lee1,2, Robert A H van de Ven1,2, Elma Zaganjor1,2

  • 1Department of Cell Biology, Harvard Medical School, Boston, MA 02115.

Proceedings of the National Academy of Sciences of the United States of America
|June 20, 2018
PubMed

Insights

SIRT3, a mitochondrial deacetylase, regulates cancer cell migration by controlling reactive oxygen species (ROS). Down-regulation of SIRT3 increases ROS, promoting metastasis. Overexpression inhibits migration and progression in breast cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Mitochondrial Biology

Background:

  • Metastasis is the primary cause of cancer mortality.
  • Reactive oxygen species (ROS) signaling is implicated in promoting cancer metastasis.
  • Molecular pathways controlling ROS in metastasis are not well understood.

Purpose of the Study:

  • To identify molecular regulators of ROS signaling in cancer cell migration.
  • To investigate the role of SIRT3 in controlling ROS and cell migration.
  • To explore the implications of SIRT3 in breast cancer metastasis.

Main Methods:

  • Investigated SIRT3 expression during cell migration.
  • Assessed ROS levels in migrating cells.
  • Examined the effects of SIRT3 modulation on Src oxidation and focal adhesion kinase (FAK) activation.
  • Correlated SIRT3 expression with metastatic outcome in human breast cancers.

Main Results:

  • SIRT3 expression is down-regulated during cell migration, leading to increased ROS.
  • Elevated ROS due to SIRT3 down-regulation represses Src oxidation and attenuates FAK activation.
  • SIRT3 overexpression inhibits breast cancer cell migration and metastasis.
  • Human breast cancers show an inverse correlation between SIRT3 expression and metastatic outcome/Src/FAK signaling.

Conclusions:

  • SIRT3 acts as a key regulator of cell migration through its control of ROS signaling.
  • SIRT3 plays a significant role in suppressing breast cancer progression and metastasis.
  • Targeting SIRT3 may offer therapeutic strategies for reducing cancer mortality.
Keywords:
SIRT3cancercell migrationmetabolismmitochondria

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