PMID- 21209554 OWN - NLM STAT- MEDLINE DCOM- 20110718 LR - 20211020 IS - 2092-6413 (Electronic) IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 43 IP - 2 DP - 2011 Feb 28 TI - Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion. PG - 111-20 AB - Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the cell-based screening assay, (-)epigallocatechin-3-gallate (EGCG) inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering and uPA activation (IC50=15.8 microgram/ml). Further analysis revealed that EGCG at low doses specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met but not epidermal growth factor (EGF)-induced phosphorylation of EGF receptor (EGFR). On the other hand, high-dose EGCG decreased both Met and EGFR proteins. We also found that EGCG did not act on the intracellular portion of Met receptor tyrosine kinase, i.e., it inhibited InlB-dependent activation of Met but not NGF-induced activation of Trk-Met hybrid receptor. This inhibition decreased HGF-induced migration and invasion by parental or HGF/SF-transfected B16F10 melanoma cells in vitro in either a paracrine or autocrine manner. Furthermore, EGCG inhibited the invasion/metastasis of HGF/SF-transfected B16F10 melanoma cells in mice. Our data suggest the possible use of EGCG in human cancers associated with dysregulated paracrine or autocrine HGF/SF-Met signaling. FAU - Kwak, In-hae AU - Kwak IH AD - Department of Biochemistry, Ajou University Medical School, Suwon, Korea. FAU - Shin, Yun-Hye AU - Shin YH FAU - Kim, Myeongdeok AU - Kim M FAU - Cha, Hyun-Young AU - Cha HY FAU - Nam, Hyun-Ja AU - Nam HJ FAU - Lee, Bok-Soon AU - Lee BS FAU - Chaudhary, S C AU - Chaudhary SC FAU - Pai, Ki-Soo AU - Pai KS FAU - Lee, Jae-Ho AU - Lee JH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (Receptors, Growth Factor) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Animals MH - Autocrine Communication/*drug effects MH - Catechin/*analogs & derivatives/metabolism/pharmacology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Female MH - *Hepatocyte Growth Factor MH - Humans MH - Mice MH - Mice, Inbred BALB C MH - Neoplasms, Experimental/*metabolism/pathology MH - Paracrine Communication/*drug effects MH - Phosphorylation/drug effects MH - Proto-Oncogene Proteins c-met/antagonists & inhibitors/metabolism MH - Receptors, Growth Factor/antagonists & inhibitors/metabolism MH - Signal Transduction PMC - PMC3047192 EDAT- 2011/01/07 06:00 MHDA- 2011/07/19 06:00 PMCR- 2011/02/28 CRDT- 2011/01/07 06:00 PHST- 2011/01/07 06:00 [entrez] PHST- 2011/01/07 06:00 [pubmed] PHST- 2011/07/19 06:00 [medline] PHST- 2011/02/28 00:00 [pmc-release] AID - emm.2010.43.013 [pii] AID - 10.3858/emm.2011.43.2.013 [doi] PST - ppublish SO - Exp Mol Med. 2011 Feb 28;43(2):111-20. doi: 10.3858/emm.2011.43.2.013.