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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
Author(s) -
Lin MengLiang,
Lu YaoCheng,
Chen HungYi,
Lee ChuanChun,
Chung JingGung,
Chen ShihShun
Publication year - 2014
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.21984
Subject(s) - lipid raft , rac1 , biology , protein kinase b , pi3k/akt/mtor pathway , microbiology and biotechnology , curcumin , signal transduction , cancer research , cell migration , cell , biochemistry
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.