title: Prostaglandin E₂ receptor EP2 mediates Snail expression in hepatocellular carcinoma cells.
abstract: Prostaglandin E2 (PGE2) has been shown to influence cell invasion and metastasis in several types of cancer, including hepatocellular carcinoma (HCC). however, the molecular mechanisms underlying it remain to be further elucidated. Snail, as one of key inducers of epithelial-mesenchymal transition (EMT), plays pivotal roles in HCC invasion and metastasis. The present study was designed to evaluate the possible signaling pathways through which PGE2 regulates Snail protein expression in HCC cell lines. PGE2 markedly enhanced Huh-7 cell invasion and migration ability by upregulating the expression level of Snail protein, and EP2 receptor played an important role in this process. Src, EGFR, Akt and mTOR were all activated and involved in the regulation of snail protein expression. Our findings suggest that PGE2 could upregulate the expression level of Snail protein through the EP2/Src/EGFR/Akt/mTOR pathway in Huh-7 cells, which promotes HCC cell invasion and migration.
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shan-Yu
authors.initials: SY
authors.lastname: Cheng
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shu-Kai
authors.initials: SK
authors.lastname: Xia
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Bai
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Rong
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Ming-Zhan
authors.initials: MZ
authors.lastname: Du
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qin-Yi
authors.initials: QY
authors.lastname: Yang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000096:biosynthesis; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation; D019061:src-Family Kinases / Q000096:biosynthesis
chemical_list: D058307:Receptors, Prostaglandin E, EP2 Subtype; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D015232:Dinoprostone