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Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway

Rintaro Okoshi1, Chung-Li Shu, Sayoko Ihara

  • 1Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan, Republic of China.

Plos One
|January 12, 2013
PubMed

Insights

Heregulin-β1 destabilizes cell junctions by affecting F-actin and adherent proteins. p38 MAP kinase inhibition reassembles junctions and promotes cell re-aggregation, revealing its role in cell adhesion.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Heregulin (HRG) β1 signaling is known to promote cell scattering by disrupting cell-cell junctions.
  • Adherens and tight junctions are crucial for maintaining tissue integrity and cell adhesion.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which HRG-β1 signaling induces cell scattering.
  • To identify the specific signaling pathways involved in junction destabilization and cell scattering.
  • To investigate the role of p38 MAP kinase in regulating cell-cell adhesion and re-aggregation.

Main Methods:

  • MCF7 cells were stimulated with HRG-β1.
  • F-actin dynamics and adherent protein localization were analyzed.
  • Specific pathway inhibitors (MEK1 and p38 MAP kinase inhibitors) were used.
  • Cell scattering and re-aggregation were monitored.

Main Results:

  • HRG-β1 stimulation destabilized the F-actin backbone of junctions before adherent protein loss.
  • MEK1 pathway activity was required for F-actin disappearance from junctions.
  • p38 MAP kinase activity was essential for HRG-β1-induced cell scattering.
  • p38 MAP kinase inhibition led to rapid reassembly of adherens and tight junctions, causing cell re-aggregation.

Conclusions:

  • p38 MAP kinase signaling directly regulates adherens junction protein dynamics.
  • p38 MAP kinase plays a critical role in controlling cell scattering and cell-cell adhesion.
  • Targeting p38 MAP kinase can reverse HRG-β1-induced cell scattering and promote cell re-aggregation.

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