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The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5

Vignesh Sundararajan1,2,3, Nicolas Gengenbacher4, Marc P Stemmler5

  • 1Department of Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany.

Oncotarget
|September 4, 2015
PubMed

Insights

The ZEB1/miR-200 feedback loop regulates cancer cell invasion by controlling TKS5 and MYLK. These genes promote invadopodia formation, crucial for tumor metastasis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Epithelial to mesenchymal transition (EMT) drives cancer invasion and metastasis.
  • ZEB1 is an EMT-inducer, antagonized by the microRNA-200 family in a feedback loop.
  • EMT involves significant changes in the actin cytoskeleton.

Purpose of the Study:

  • To elucidate the role of the ZEB1/miR-200 feedback loop in controlling tumor cell invasion.
  • To identify novel targets of miR-200c involved in EMT and cancer metastasis.

Main Methods:

  • In silico screening of actin-interacting proteins.
  • Analysis of gene co-expression in cancer cell lines and patient samples.
  • Depletion of TKS5 and MYLK in breast cancer cells to assess invasive potential and invadopodia formation.

Main Results:

  • TKS5 and MYLK were identified as novel miR-200c targets.
  • Co-expression of TKS5 and MYLK with ZEB1 correlated with low miR-200c levels in cancer.
  • Depletion of TKS5 or MYLK reduced breast cancer cell invasion and invadopodia formation.
  • MYLK was identified as a novel player in invadopodia formation.

Conclusions:

  • TKS5 and MYLK are mediators of cancer cell invasion regulated by the ZEB1/miR-200 feedback loop.
  • Targeting TKS5 and MYLK may offer therapeutic strategies against cancer metastasis.
Keywords:
MYLK (MLCK)ZEB1epithelial to mesenchymal transition (EMT)invadopodiamiR-200

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