title: PGE2 promotes renal carcinoma cell invasion through activated RalA.
abstract: Incidence of kidney cancer is on the rise, and a better understanding of molecular mechanisms involved in the cancer invasion and metastasis is required for the development of curative therapeutics. In this study, we report that the proinflammatory cytokine prostaglandin E2 (PGE2) induces the malignant SN12C, but not benign HK2 kidney cell invasion. The PGE2 increases SN12C cell invasion through a signal pathway that encompasses EP2 and EP4, Akt, small GTPase RalA and Ral·GTP inactivator RGC2. The results support the idea that targeted interference of EP2/EP4 signal to RalA·GTP may provide benefit to patients diagnosed with advanced kidney cancer.
authors.affiliation: Department of Urology and Prostate Disease Center, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: W J
authors.initials: WJ
authors.lastname: Kim
authors.forename: Y
authors.initials: Y
authors.lastname: Daaka
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism / Q000502:physiology; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020725:ral GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D051057:Proto-Oncogene Proteins c-akt; C492198:RALA protein, human; D020725:ral GTP-Binding Proteins; D015232:Dinoprostone