Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling

Jianjun Han, Lu Zhang, Hui Guo, Weiya Z. Wysham, Dario R. Roque, Adam K. Willson, Xiugui Sheng, Chunxiao Zhou*, Victoria L. Bae-Jump

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Objectives Obesity and diabetes are well-known risk factors for the development of endometrial cancer. A high rate of aerobic glycolysis represents a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. This study aimed to investigate the effect of various concentrations of glucose on cell proliferation in endometrial cancer. Methods ECC-1 and Ishikawa cells were treated with low glucose (1 mM), normal glucose (5 mM) and high glucose (25 mM), and cytotoxicity, apoptosis, cell cycle, adhesion/invasion, and changes of AMPK/mTOR/S6 and MAPK pathways were evaluated. Results Our results revealed that high glucose increased cell growth and clonogenicity in two endometrial cancer cell lines in a dose dependent manner. Low glucose induced the activity of cleaved caspase 3 and caused cell cycle G1 arrest. High glucose increased the ability of adhesion and invasion by decreasing E-cadherin and increasing Snail expression. In addition, high glucose increased glucose uptake and glycolytic activity through modulating the AMPK/mTOR/S6 and MAPK pathways. Conclusions Our findings suggest that glucose stimulated cell proliferation through multiple complex signaling pathways. Targeting glucose metabolism may be a promising therapeutic strategy in the treatment of endometrial cancer.

Original languageEnglish (US)
Pages (from-to)668-675
Number of pages8
JournalGynecologic oncology
Volume138
Issue number3
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

Keywords

  • Endometrial cancer
  • Glucose
  • Glycolysis
  • Invasion

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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