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Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells

Authors

  • Meng-Liang Lin,

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
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  • Yao-Cheng Lu,

    1. Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan
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  • Hung-Yi Chen,

    1. Graduate Institute of Pharmacy, China Medical University, Taichung, Taiwan
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  • Chuan-Chun Lee,

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
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  • Jing-Gung Chung,

    1. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
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  • Shih-Shun Chen

    Corresponding author
    1. Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan
    • Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, No. 666, Buzih Road, Beitun District, Taichung 40601, Taiwan.

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  • Conflict of interest: None.

Abstract

Stromal cell-derived factor-1α (SDF-1α) is a ligand for C-X-C chemokine receptor type 4 (CXCR4), which contributes to the metastasis of cancer cells by promoting cell migration. Here, we show that the SDF-1α/CXCR4 axis can significantly increase invasion of esophageal carcinoma (EC) cells. We accomplished this by examining the effects of CXCR4 knockdown as well as treatment with a CXCR4-neutralizing antibody and the CXCR4-specific inhibitor AMD3100. Curcumin suppressed SDF-1α-induced cell invasion and matrix metalloproteinase-2 (MMP-2) promoter activity, cell surface localization of CXCR4 at lipid rafts, and lipid raft-associated ras-related C3 botulinum toxin substrate 1 (Rac1)/phosphatidylinositol 3-kinase (PI3K) p85α/Akt signaling. Curcumin inhibited SDF-1α-induced cell invasion by suppressing the Rac1–PI3K signaling complex at lipid rafts but did not abrogate lipid raft formation. We further demonstrate that the attenuation of lipid raft-associated Rac1 activity by curcumin was critical for the inhibition of SDF-1α-induced PI3K/Akt/NF-κB activation, cell surface localization of CXCR4 at lipid rafts, MMP-2 promoter activity, and cell invasion. Collectively, our results indicate that curcumin inhibits SDF-1α-induced EC cell invasion by suppressing the formation of the lipid raft-associated Rac1-PI3K-Akt signaling complex, the localization of CXCR4 with lipid rafts at the cell surface, and MMP-2 promoter activity, likely through the inhibition of Rac1 activity. © 2012 Wiley Periodicals, Inc.

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