Green tea Polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor
Green tea Polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor
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DOI：
10.1074/jbc.m707892200
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发表时间：
2008-02-08
影响因子：
4.8
通讯作者：
Tachibana, Hirofumi
中科院分区：
文献类型：
--
作者：
Umeda, Daisuke;Yano, Satomi;Tachibana, Hirofumi
(-)-表没食子儿茶素-3-没食子酸酯 (EGCG) 是绿茶中的主要多酚，已被证明是一种有效的化学预防剂。最近，67-kDa 层粘连蛋白受体 (67LR) 已被确定为 EGCG 的细胞表面受体，介导 EGCG 的抗癌活性。事实上，67LR 的表达赋予了 EGCG 对肿瘤细胞的反应性；然而，EGCG 体内抗癌活性的分子基础尚不完全清楚。在这里，我们表明：(i) 使用直接遗传筛选，真核翻译延伸因子 1A (eEF1A) 被鉴定为负责 EGCG 抗癌活性的成分； (ii) 通过 eEF1A 和 67LR，EGCG 诱导肌球蛋白磷酸酶靶向亚基 1 (MYPT1) 在 Thr-696 处去磷酸化并激活肌球蛋白磷酸酶； (iii) 肿瘤细胞中 67LR、eEF1A 或 MYPT1 的沉默导致 EGCG 诱导的体内肿瘤生长抑制作用消失。此外，我们发现 EGCG 通过 67LR 上调 eEF1A。总体而言，这些发现表明 eEF1A 和 MYPT1 都参与了通过 67LR 预防癌症的 EGCG 信号传导。
(-)-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.