Home
Resources
Publications
Metformin Inhibits 17β-estradiol-induced Epithelial-To-Mesenchymal Transition via βKlotho-related ERK1/2 Signaling and AMPKα Signaling in Endometrial Adenocarcinoma Cells

Metformin Inhibits 17β-estradiol-induced Epithelial-To-Mesenchymal Transition via βKlotho-related ERK1/2 Signaling and AMPKα Signaling in Endometrial Adenocarcinoma Cells

Zhao Liu, Shasha Qi, Xingbo Zhao, Mingjiang Li, Sentai Ding, Jiaju Lu, Hui Zhang

Oncotarget. 2016 Apr 19;7(16):21315-31.

PMID: 26824324

Abstract:

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP571926	Estradiol Related Compound C		571-92-6	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: