title: Peroxisome proliferator-activated receptor γ upregulates galectin-9 and predicts prognosis in intestinal-type gastric 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 lentiviral constructs. Interaction between PPARγ and galectin-9 was evaluated using luciferase and chromatin immunoprecipitation 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 hazard ratio, 0.42; 95% CI, 0.22-0.81). PPARγ inhibits cell invasion, migration and epithelial-mesenchymal transition through upregulation of galectin-9 in vitro and in vivo.
authors: Center for Gastric Cancer, National Cancer Center, Gyeonggi, Republic of Korea.
authors: Soo-Jeong
authors: SJ
authors: Cho
authors: Myeong-Cherl
authors: MC
authors: Kook
authors: Jun Ho
authors: JH
authors: Lee
authors: Ji-Young
authors: JY
authors: Shin
authors: JuRi
authors: J
authors: Park
authors: Young-Ki
authors: YK
authors: Bae
authors: Il Ju
authors: IJ
authors: Choi
authors: Keun Won
authors: KW
authors: Ryu
authors: Young-Woo
authors: YW
authors: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition; D037161:Galectins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011485:Protein Binding; D000077154:Rosiglitazone; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology; D015854:Up-Regulation; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D037161:Galectins; C105032:LGALS9 protein, human; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: galectin-9; gastric cancer; intestinal-type gastric cancer; peroxisome proliferator-activated receptor γ (PPARγ); prognosis; survival