Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor.
(-)-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.
Umeda
Daisuke
D
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Yano
Satomi
S
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Yamada
Koji
K
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Tachibana
Hirofumi
H
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan; Laboratory of Functional Food Design, Department of Functional Metabolic Design, Bio-Architecture Center, Kyushu University, Fukuoka 812-8581, Japan. Electronic address: tatibana@agr.kyushu-u.ac.jp.
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D043263:Myosin-Light-Chain Phosphatase / Q000502:physiology; D020648:Peptide Elongation Factor 1 / Q000502:physiology; D010636:Phenols / Q000737:chemistry*; D010766:Phosphorylation; D059808:Polyphenols; D017474:Receptors, Laminin / Q000737:chemistry*; D015398:Signal Transduction
D016588:Anticarcinogenic Agents; C094814:EEF1A1 protein, human; D005419:Flavonoids; D020648:Peptide Elongation Factor 1; D010636:Phenols; D059808:Polyphenols; D017474:Receptors, Laminin; D002392:Catechin; C045651:epigallocatechin gallate; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human