Enterolobium contortisiliquum Trypsin Inhibitor (EcTI), a Plant Proteinase Inhibitor, Decreases in Vitro Cell Adhesion and Invasion by Inhibition of Src Protein-Focal Adhesion Kinase (FAK) Signaling Pathways*

C. D. De Paula,V. Coulson-Thomas,J. G. Ferreira,P. K. Maza,E. Suzuki,A. Nakahata,H. Nader,M. Sampaio,M. Oliva

Published 2011 in Journal of Biological Chemistry

ABSTRACT

Background: The effect of Enterolobium contortisiliquum trypsin inhibitor (EcTI) on the adhesion, migration, and invasion of gastric cancer cells. Results: EcTI inhibited adhesion, migration, and cell invasion and decreased Src-FAK signaling. Conclusion: EcTI inhibits the invasion of gastric cancer cells through alterations in integrin-dependent cell signaling pathways. Significance: Inhibition of invadopodia formation may be an attractive approach for cancer therapy. Tumor cell invasion is vital for cancer progression and metastasis. Adhesion, migration, and degradation of the extracellular matrix are important events involved in the establishment of cancer cells at a new site, and therefore molecular targets are sought to inhibit such processes. The effect of a plant proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on the adhesion, migration, and invasion of gastric cancer cells was the focus of this study. EcTI showed no effect on the proliferation of gastric cancer cells or fibroblasts but inhibited the adhesion, migration, and cell invasion of gastric cancer cells; however, EcTI had no effect upon the adhesion of fibroblasts. EcTI was shown to decrease the expression and disrupt the cellular organization of molecules involved in the formation and maturation of invadopodia, such as integrin β1, cortactin, neuronal Wiskott-Aldrich syndrome protein, membrane type 1 metalloprotease, and metalloproteinase-2. Moreover, gastric cancer cells treated with EcTI presented a significant decrease in intracellular phosphorylated Src and focal adhesion kinase, integrin-dependent cell signaling components. Together, these results indicate that EcTI inhibits the invasion of gastric cancer cells through alterations in integrin-dependent cell signaling pathways.

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