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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Morphological transformation induced by activation of the mitogen-activated protein kinase pathway requires

M W Strobeck1, M Okuda, H Yamaguchi

  • 1Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA.

The Journal of Biological Chemistry
|May 21, 1999
PubMed

Insights

Oncogenes like Ras activate the MAPK pathway, inhibiting T-type calcium channels and altering cell shape. This study reveals T-type calcium channel suppression is key to cancer cell morphology changes.

Area of Science:

  • Cell Biology
  • Oncology
  • Molecular Biology

Background:

  • Oncogene activation, such as by Ras, induces fibroblast morphological changes crucial for cancer malignancy.
  • The mitogen-activated protein kinase (MAPK) pathway is a common downstream target of oncogenes.
  • Intracellular calcium, regulated by T- and L-type channels, influences cell morphology.

Purpose of the Study:

  • To investigate the role of T-type calcium channels in oncogene-induced fibroblast transformation.
  • To determine the relationship between MAPK pathway activation and T-type calcium channel function.
  • To elucidate the contribution of T-type calcium channel suppression to cancer cell morphology.

Main Methods:

  • Utilized oncogenically activated Ras and mutant MEK in fibroblast cell models.
  • Assessed T-type calcium channel currents in response to oncogene and pathway activation.
  • Employed a MEK-specific inhibitor and a T-type calcium channel antagonist.

Main Results:

  • T-type calcium channel currents were inhibited in cells expressing activated Ras or mutant MEK.
  • MEK inhibition restored T-type calcium channel activity in ras-transformed cells.
  • Suppression of T-type calcium channels by the MAPK pathway is essential for transformation-associated morphological changes.

Conclusions:

  • The MAPK pathway, activated by oncogenes, suppresses T-type calcium channels.
  • Inhibition of T-type calcium channels is a critical step in oncogene-induced cell transformation and cancer progression.
  • Targeting T-type calcium channels may offer a novel therapeutic strategy for cancers driven by these oncogenic pathways.

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