title: Urocortin affects migration of hepatic cancer cell lines via differential regulation of cPLA2 and iPLA2.
abstract: Urocortin (UCN) is a member of corticotrophin-releasing factor (CRF) family, which has been reported to play a role in many biological processes, including inflammation and cancer development. Growing evidence shows that PLA2 (phospholipase A2) enzymes also participate in inflammation and tumor development. The primary aim of the present study was to identify a novel signaling pathway of CRF receptor activation leading to migration of two kinds of hepatoma carcinoma cell lines, HepG2 and SMMC-7721, linking the stimulation of PLA2 expression by UCN to UCN-induced tumor cell migration. Pharmacological inhibitors and genetic approaches (such as stable transfection and siRNAs) were used in this study. Unlike HepG2 cells which express both CRF receptors themselves, SMMC-7721 cells which hardly express these two CRF receptors needed stable transfection with CRFR1 or CRFR2 to observe the effect of UCN. Two types of PLA2 enzymes, cPLA2 and iPLA2, were found to be regulated by UCN. Our data showed that UCN raised cPLA2 expression but lowered iPLA2 expression. Moreover, UCN was found to act on the certain region of iPLA2 promoter to reduce its transcription. UCN promoted tumor cell migration by up-regulating cPLA2 expression via CRFR1 whereas it suppressed tumor cell migration by down-regulating iPLA2 expression via CRFR2. These results indicate the dual roles for UCN in the hepatoma carcinoma cell migration, which involve the regulation of both cPLA2and iPLA2.
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors: Chao
authors: C
authors: Zhu
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors: Zongxing
authors: Z
authors: Sun
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors: Chuanhua
authors: C
authors: Li
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors: Rui
authors: R
authors: Guo
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors: Li
authors: L
authors: Li
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors: Lai
authors: L
authors: Jin
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors: Rong
authors: R
authors: Wan
authors: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China. Electronic address: snli@njmu.edu.cn.
authors: Shengnan
authors: S
authors: Li
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D054512:Phospholipases A2, Calcium-Independent / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011753:Pyrones / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054832:Urocortins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D009281:Naphthalenes; D011753:Pyrones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D054512:Phospholipases A2, Calcium-Independent; D054510:Phospholipases A2, Cytosolic
keywords: CRF receptors; Cell migration; PLA2; Urocortin