(؊)-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.Many of the current anticancer drugs are natural products or derivatives thereof, illustrating the utility of natural products in drug discovery (1, 2). Green tea has been shown to have cancerpreventive activity in a variety of organ sites in animal models (3-5) and humans (6). Among the green tea constituents, (Ϫ)-epigallocatechin-3-gallate (EGCG) 2 is the most abundant and most active constituent in inhibiting experimental carcinogenesis and related reactions. Although many mechanisms for the anticancer activities of EGCG have been proposed based mainly on studies in cell lines (4, 7), it is still not clear which EGCG-induced molecular events are responsible for its cancerpreventive activity in vivo. Recently, we have identified 67-kDa laminin receptor (67LR) as a cell surface EGCG receptor that mediates the anticancer action of EGCG (8), and others showed that RNAi-mediated silencing of 67LR results in abrogation of EGCG-induced apoptosis in myeloma cells (9).67LR is a nonintegrin laminin receptor and known to be overexpressed on the cell surface of various tumor cells (10). The expression level of this protein strongly correlates with the risk of tumor invasion and metastasis (10 -12). Thus, it was postulated that 67LR plays a significant role in the tumor progression and speculated that studies conducted to define the function of 67LR could provide a new approach to cancer prevention. In this study, we tried to illuminate the cell signaling pathway mediated after the binding of EGCG to 67LR and its biologic and physiologic significance for the cancer-preventive activity of EGCG in vivo.In an attempt to elucidate the pathways involved in the anticancer action of EGCG, we applied genetic suppressor element (GSE) methodology. GSEs are short cDNA fragments encoding peptides acting as dominant inhibitors of protein function or antisense RNAs inhibiting gene expression (13). GSEs behave as dominant selectable markers for the ph...

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Lung cancer is a common type of cancer that represents a health problem worldwide; lung adenocarcinoma (LUAD) is a major subtype of lung cancer. Although several treatments for LUAD have been developed, the mortality rate remains high because of uncontrollable progression. Further biological and clinicopathological studies are therefore needed. Here, we investigated the role of family with sequence similarity 111 member B (FAM111B), which is highly expressed in papillary‐predominant LUAD; however, its role in cancer is unclear. An immunohistochemical analysis confirmed that papillary‐predominant adenocarcinomas exhibited higher expression of FAM111B, compared with lepidic‐predominant adenocarcinomas. Additionally, FAM111B expression was significantly correlated with clinical progression. In vitro functional analyses using FAM111B‐knockout cells demonstrated that FAM111B plays an important role in proliferation and cell cycle progression of KRAS ‐driven LUAD under serum‐starvation conditions. Furthermore, FAM111B regulated cyclin D1‐CDK4‐dependent cell cycle progression by degradation of p16. In summary, we revealed the clinical importance of FAM111B in human tumor tissues, as well as its function as a degradative enzyme. Therefore, FAM111B has potential as a clinicopathological prognostic marker for LUAD.

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The results suggest that the diet containing one of the two flavones might suppress the up-regulation of serum IgE induced by OVA-immunization through the suppression of Th2-type immune response.