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TIS21/BTG2 inhibits invadopodia formation by downregulating reactive oxygen species level in MDA-MB-231 cells

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Abstract

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.

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Abbreviations

ROS:

Reactive oxygen species

MEF:

Mouse embryonic fibroblast

NAC:

N-acetyl-l-cysteine

FBS:

Fetal bovine serum

ECM:

Extracellular matrix

TIS21:

12-O-tetradecanoylphorbol-13-acetate-inducible sequence 21

BTG2:

B-cell translocation gene 2

Ad-TIS21:

Adenovirus carrying TIS21 cDNA

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgments

Authors greatly appreciate careful reading of this manuscript by Prof. Woon Ki Paik in Ajou University School of Medicine. This work was supported by the grants of the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A121725) and the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (131280).

Conflict of interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Brain Korea 21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon, 443-721, Korea

    Jung-A. Choi & In Kyoung Lim

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  1. Jung-A. Choi
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  2. In Kyoung Lim
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Correspondence to In Kyoung Lim.

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Choi, JA., Lim, I.K. TIS21/BTG2 inhibits invadopodia formation by downregulating reactive oxygen species level in MDA-MB-231 cells. J Cancer Res Clin Oncol 139, 1657–1665 (2013). https://doi.org/10.1007/s00432-013-1484-3

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  • DOI: https://doi.org/10.1007/s00432-013-1484-3

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