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Utilization of the Soft Agar Colony Formation Assay to Identify Inhibitors of Tumorigenicity in Breast Cancer Cells
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Utilization of the Soft Agar Colony Formation Assay to Identify Inhibitors of Tumorigenicity in Breast Cancer Cells

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Inhibition of breast cancer invasion by TIS21/BTG2/Pc3-Akt1-Sp1-Nox4 pathway targeting actin nucleators, mDia genes

J-A Choi1, Y S Jung2, J Y Kim2

  • 1Departments of Biochemistry and Molecular Biology, Ajou University School of Medicine, and Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea.

Oncogene
|March 24, 2015
PubMed

Insights

Tumor suppressor TIS21 inhibits breast cancer cell invasion by downregulating NADPH oxidase 4 (Nox4)-derived ROS. This pathway involves Akt1 activation, reducing Sp1-mediated Nox4 transcription and subsequently mDia gene expression.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Mammalian diaphanous (mDia) proteins regulate actin dynamics, impacting cancer cell invasion and metastasis.
  • Tumor suppressor TIS21 inhibits invadopodia formation by reducing reactive oxygen species (ROS) in MDA-MB-231 cells.

Purpose of the Study:

  • To investigate the mechanism by which TIS21 inhibits breast cancer cell invasion.
  • To elucidate the role of the Akt1/Nox4/ROS signaling axis in TIS21-mediated inhibition of invasion.

Main Methods:

  • RNA interference to knockdown Akt1.
  • Analysis of F-actin remodeling, ROS generation, and Nox4 expression.
  • Investigation of Sp1-mediated Nox4 transcription.

Main Results:

  • TIS21 downregulates diaphanous-related formin (DRF) expression by reducing NADPH oxidase 4 (Nox4)-derived ROS via Akt1 activation.
  • Akt1 knockdown reversed TIS21-induced inhibition of F-actin remodeling and ROS generation.
  • TIS21-Akt1 signaling downregulated Sp1-mediated Nox4 transcription, inhibiting cancer cell invasion.

Conclusions:

  • TIS21 inhibits breast cancer cell invasion by targeting the Sp1-Nox4-ROS cascade through Akt1 activation.
  • This pathway subsequently reduces invasion activity by inhibiting mDia family genes, offering a novel therapeutic target.

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