文献类型：期刊文献

英文题名：Suppression of GOLM1 by EGCG through HGF/HGFR/AKT/GSK-3β/β-catenin/c-Myc signaling pathway inhibits cell migration of MDA-MB-231

作者：Xie, Ling[1];Yi, Jun[1];Song, Yongjia[1];Zhao, Mengyao[1];Fan, Liqiang[1];Zhao, Liming[1,2]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg Technol SC, Shanghai 200237, Peoples R China

年份：2021

卷号：157

外文期刊名：FOOD AND CHEMICAL TOXICOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000706869300002)】；

基金：This work was supported by the National Key R&D Program of China [grant number 2019YFD0901805], the 111 Project (B18022), the Fundamental Research Funds for the Central Universities [grant number 22221818014], and the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, ECUST (ZDXM2019).

语种：英文

外文关键词：GOLM1; Epigallocatechin-3-Gallate; Migration; MDA-MB-231

摘要：Golgi Membrane Protein 1 (GOLM1) has been identified as a prime target for cancer therapy because it overexpresses in many solid tumors, increases tumor growth and metastasis and leads to unfavorable survival. Though various approaches including siRNA interference and antibody targeting have been attempted, GOLM1 has remained an un-targetable molecule because of its mainly intracellular location and the lack of domains that could possibly be interfered with by small molecules. Numerous natural anti-tumoral plant substances have been identified, while their possible function on GOLM1 has never been revealed. This is the first report to study the relationship between GOLM1 downregulation and natural anti-tumoral plant substances and the possible mechanism. Among three tested possible migration-inhibiting natural substances (Epigallocatechin gallate (EGCG), Betulinic acid (BA) and Lupeol), EGCG showed the most potent inhibition effect on GOLM1 expression and MDA-MB-231 cell migration. Knocking down GOLM1 expression further increased the EGCG treatment effect. Molecular docking prediction and following experiments suggested that EGCG may inhibit GOLM1 expression and MDA-MB-231 cells migration through HGF/HGFR/AKT/GSK-3/ beta-catenin/c-Myc signaling pathway. In all, EGCG is the first identified GOLM1 downregulation natural product. Silencing GOLM1 may be a novel mechanism of potentiated anti-cancer migration effects and cytotoxic effect of EGCG. In addition, this study shed a new way for cancer therapy by combination of GOLM1 silencing and EGCG treatment in the future.