Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells

Oncotarget
Zhao LiuHui Zhang

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, met...Continue Reading

References

Jun 5, 2003·Lancet·Paul HardimanWilliam Atiomo
Mar 31, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ingunn M StefanssonLars A Akslen
Aug 26, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Loren K MellArno J Mundt
Mar 29, 2006·The Journal of Cell Biology·Jonathan M LeeErik W Thompson
May 20, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Meenakshi SinghJennifer K Richer
Dec 10, 2008·Molecular and Cellular Endocrinology·Hiroshi Kurosu, Makoto Kuro-O
Jun 3, 2009·The Journal of Clinical Investigation·Michael Zeisberg, Eric G Neilson
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Jul 1, 2010·Diabetes Care·Edward GiovannucciDouglas Yee
Nov 29, 2011·Clinical Science·Benoit ViolletFabrizio Andreelli
Feb 2, 2012·International Journal of Breast Cancer·Sudipa Saha Roy, Ratna K Vadlamudi
Apr 18, 2012·Gynecologic Oncology·Kristy K WardSteven C Plaxe
Jan 9, 2013·Journal of the National Cancer Institute·Hannah AremCharles E Matthews
Jan 16, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elisabeth WikHelga B Salvesen
Mar 19, 2013·European Journal of Pharmacology·Christos V Rizos, Moses S Elisaf
Nov 26, 2013·Gynecologic Oncology·Emily M KoVictoria Bae-Jump
Jan 8, 2014·Nature Reviews. Endocrinology·Ida Pernicova, Márta Korbonits
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Mar 20, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Li LiYong He
Apr 10, 2015·Cancer Research·Reetta VirtakoivuJohanna Ivaska
Sep 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Teresa HelstenRazelle Kurzrock

❮ Previous
Next ❯

Citations

Jul 28, 2016·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Hui ZhangXingbo Zhao
May 11, 2016·Pharmaceuticals·Panagiota PapanagnouMaria Tsironi
Feb 6, 2017·Journal of Cellular Physiology·Soumaya Allouch, Shankar Munusamy
Sep 14, 2018·Frontiers in Oncology·Teresa Y LeeJennifer M Johnson
May 14, 2020·Cancers·Frances L ByrneRhonda Farrell
Dec 30, 2020·Cancers·Ludwig KieselMichael Eichbaum
Nov 11, 2021·Journal of Drug Targeting·Bartłomiej BarczyńskiJan Kotarski

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
phase contrast microscopy
biopsies
Transfection
scraping

Software Mentioned

SPSS
CellQuest Pro

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis