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Updated: May 9, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TIS21/BTG2 inhibits invadopodia formation by downregulating reactive oxygen species level in MDA-MB-231 cells
1Department of Biochemistry and Molecular Biology, Brain Korea 21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon, 443-721, Korea.
Purpose:
Invasion of cancer cells depends on the proteolytic degradation of extracellular matrix regulated by actin-driven membrane protrusions, called invadopodia. However, the mechanisms underlying invadopodia formation in cancer cells remain largely unknown.
Methods:
By employing adenoviral transduction of breast cancer cells with either β-galactosidase (Ad-LacZ) or TIS21(/BTG2/Pc3) (Ad-TIS21) gene, the regulation of invadopodia formation was investigated. Invasion activity was examined by invadopodia assay and Matrigel assay. Intracellular reactive oxygen species (ROS) was monitored by FACS-based analysis.
Results:
Here, we observed that TIS21 suppressed invadopodia formation as well as invasion activity along with F-actin remodeling. The inhibition of TIS21-mediated invadopodia formation was accompanied with attenuation of ROS generation in the TIS21 expressers, indicating that TIS21-mediated inhibition of ROS plays a critical role for invadopodia formation by regulating actin-associated protein remodeling. This was further confirmed in the TIS21(-/-)MEF cells.
Conclusions:
This is the first report to provide insight into invasion signals regulated by tumor suppressor, TIS21(/BTG2/Pc3) gene, in the intractable breast cancer cells.
Insights
The tumor suppressor TIS21 inhibits breast cancer cell invasion by suppressing invadopodia formation and reducing reactive oxygen species (ROS). This finding offers new insights into controlling cancer cell metastasis.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Cancer cell invasion relies on invadopodia, which degrade the extracellular matrix.
- The precise mechanisms governing invadopodia formation in cancer cells are not fully understood.
Purpose of the Study:
- To investigate the role of TIS21 in regulating invadopodia formation and cancer cell invasion.
- To explore the involvement of reactive oxygen species (ROS) in TIS21-mediated invasion suppression.
Main Methods:
- Adenoviral transduction of breast cancer cells with Ad-LacZ or Ad-TIS21.
- Assessment of invasion activity using invadopodia and Matrigel assays.
- Monitoring intracellular ROS levels via FACS-based analysis.
Main Results:
- TIS21 significantly suppressed invadopodia formation, invasion, and F-actin remodeling.
- TIS21 expression led to reduced ROS generation, crucial for invadopodia formation.
- These effects were confirmed in TIS21-deficient mouse embryonic fibroblast (MEF) cells.
Conclusions:
- TIS21 acts as a suppressor of invadopodia formation and cancer cell invasion.
- TIS21-mediated inhibition of ROS is a key mechanism regulating invadopodia formation.
- This study provides novel insights into invasion signaling pathways involving the tumor suppressor TIS21 in breast cancer.
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