PUBLICATION

Peroxisome Proliferator-Activated Receptor γ Up-regulates Galectin-9 and Predicts Prognosis in Intestinal-Type Gastric Cancer

Authors
Cho, S.J., Kook, M.C., Lee, J.H., Shin, J.Y., Park, J., Bae, Y.K., Choi, I.J., Ryu, K.W., Kim, Y.W.
ID
ZDB-PUB-140701-7
Date
2015
Source
International Journal of Cancer   136(4): 810-20 (Journal)
Registered Authors
Keywords
Gastric cancer, Intestinal type gastric cancer, Peroxisome proliferator-activated receptor γ (PPARγ), Prognosis, Survival, galectin-9
MeSH Terms
  • Animals
  • Antineoplastic Agents/pharmacology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival/drug effects
  • Epithelial-Mesenchymal Transition
  • Galectins/genetics*
  • Galectins/metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • PPAR gamma/agonists
  • PPAR gamma/physiology*
  • Prognosis
  • Promoter Regions, Genetic
  • Proportional Hazards Models
  • Protein Binding
  • Stomach Neoplasms/metabolism*
  • Stomach Neoplasms/mortality
  • Stomach Neoplasms/pathology
  • Thiazolidinediones/pharmacology
  • Up-Regulation
  • Zebrafish
PubMed
24976296 Full text @ Int. J. Cancer
Abstract
The importance of PPARγ (peroxisome proliferator-activated receptor γ) in gastric cancer (GC) is unclear. We investigated the role of PPARγ in GC cell lines and an animal model, and its prognostic significance of PPARγ in GC patients. We controlled PPARγ and galectin-9 expression by using siRNAs and lenti-viral constructs. Interaction between PPARγ and galectin-9 was evaluated using luciferase and ChIP assays. PPARγ expression in GCs was determined by immunohistochemical staining of tissue microarrays and survival analysis was done. Overexpression of PPARγ was accompanied by increased galectin-9. Enhanced PPARγ or galectin-9 expression increased E-cadherin expression, decreased expression of N-cadherin, fibronectin, snail, twist and slug; and reduced cell invasion and migration. PPARγ bound to the galectin-9 promoter region. Galectin-9 activity increased in PPARγ-overexpressing cells but decreased in PPARγ siRNA-treated cells. In a zebrafish xenograft model, the number of migrated cancer cells and number of fish with AGS cells in the tail vein were reduced in PPARγ-overexpressing GC cells. PPARγ was expressed in 462 of the 688 patients (69.2%) with GC. In 306 patients with intestinal-type GC, those with PPARγ-positive tumors had lower overall and cancer-specific mortalities than those with PPARγ-negative tumors. PPARγ expression was an independent prognostic factor for overall and GC-specific mortality in patients with intestinal-type GC (adjusted HR, 0.42; 95% CI, 0.22-0.81). PPARγ inhibits cell invasion, migration, and epithelial-mesenchymal transition through up-regulation of galectin-9 in vitro and in vivo.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping