Conflict of interest: None.
Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by Curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells†
Article first published online: 28 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
How to Cite
Lin, M.-L., Lu, Y.-C., Chen, H.-Y., Lee, C.-C., Chung, J.-G. and Chen, S.-S. (2012), Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by Curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells. Mol. Carcinog.. doi: 10.1002/mc.21984
- Article first published online: 28 NOV 2012
- Manuscript Accepted: 29 OCT 2012
- Manuscript Received: 20 SEP 2012
- Central Taiwan University of Science and Technology, Taiwan. Grant Number: CTU100-P-11
- China Medical University. Grant Number: CMU99-TC-26
- esophageal carcinoma;
- lipid raft;
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.