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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
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Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway

Taisuke Yoshimoto1, Takahisa Takino2, Zichen Li2

  • 1Division of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Department of Oral and Maxillofacial Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

Biochemical and Biophysical Research Communications
|December 3, 2014
PubMed

Insights

Vinculin knockdown in cancer cells reduces cell adhesion and increases migration by upregulating MT1-MMP via the MEK/ERK pathway, suggesting vinculin

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Vinculin plays a role in cellular functions, including stabilizing the tumor suppressor PTEN.
  • Its role in tumor progression beyond PTEN stabilization requires further investigation.

Purpose of the Study:

  • To investigate the role of vinculin in tumor progression independent of PTEN stabilization.
  • To elucidate the molecular mechanisms by which vinculin influences cancer cell behavior.

Main Methods:

  • Vinculin was knocked down in PTEN-deficient squamous cell carcinoma HSC-4 cells.
  • Phenotypical changes, cell adhesion, MT1-MMP expression, and cell migration were analyzed.
  • The involvement of the MEK/ERK pathway was assessed using ERK inhibition.

Main Results:

  • Vinculin knockdown led to reduced cell-cell and cell-extracellular matrix adhesions.
  • MT1-MMP expression was upregulated at the transcriptional level, enhancing cell migration.
  • Inhibition of ERK signaling abrogated the MT1-MMP transcriptional upregulation.

Conclusions:

  • Vinculin negatively regulates the malignant phenotype of tumor cells.
  • This regulation involves the MEK/ERK pathway and affects MT1-MMP transcription.
Keywords:
CancerCell–extracellular matrix adhesionMT1-MMPMigrationVinculin

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