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Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2008 Feb 08; Vol. 283 (6), pp. 3050-3058. Date of Electronic Publication: 2007 Dec 12. - Publication Year :
- 2008
-
Abstract
- (-)-Epigallocatechin-3-gallate (EGCG), the principal polyphenol in green tea, has been shown to be a potent chemopreventive agent. Recently, 67-kDa laminin receptor (67LR) has been identified as a cell surface receptor for EGCG that mediates the anticancer activity of EGCG. Indeed, expression of 67LR confers EGCG responsiveness to tumor cells; however, the molecular basis for the anticancer activity of EGCG in vivo is not entirely understood. Here we show that (i) using a direct genetic screen, eukaryotic translation elongation factor 1A (eEF1A) is identified as a component responsible for the anticancer activity of EGCG; (ii) through both eEF1A and 67LR, EGCG induces the dephosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) at Thr-696 and activates myosin phosphatase; and (iii) silencing of 67LR, eEF1A, or MYPT1 in tumor cells results in abrogation of EGCG-induced tumor growth inhibition in vivo. Additionally, we found that eEF1A is up-regulated by EGCG through 67LR. Overall, these findings implicate both eEF1A and MYPT1 in EGCG signaling for cancer prevention through 67LR.
- Subjects :
- Animals
Anticarcinogenic Agents pharmacology
Catechin chemistry
Catechin metabolism
Cell Line, Tumor
HeLa Cells
Humans
Melanoma, Experimental
Mice
Myosin-Light-Chain Phosphatase physiology
Peptide Elongation Factor 1 physiology
Phosphorylation
Polyphenols
Signal Transduction
Catechin analogs & derivatives
Flavonoids chemistry
Gene Expression Regulation, Neoplastic
Phenols chemistry
Receptors, Laminin chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 283
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18079119
- Full Text :
- https://doi.org/10.1074/jbc.M707892200