title: Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling.
abstract: OBJECTIVE
  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 (1mM), normal glucose (5mM) and high glucose (25mM), 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.
authors.affiliation: Department of Surgical Oncology, Shandong Cancer Hospital and Institute, Jinan, China; Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Han
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, China; Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, China; Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Weiya Z
authors.initials: WZ
authors.lastname: Wysham
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Dario R
authors.initials: DR
authors.lastname: Roque
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Willson
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Xiugui
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: czhou@med.unc.edu.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: victoria_baejump@med.unc.edu.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bae-Jump
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C546842:MTOR protein, human; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Endometrial cancer; Glucose; Glycolysis; Invasion