title: The Notch1/cyclooxygenase-2/Snail/E-cadherin pathway is associated with             hypoxia-induced hepatocellular carcinoma cell invasion and migration.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide;             however, the prognosis of HCC patients remains poor. This poor prognosis is mainly             attributed to the high rate of intrahepatic and distant metastasis. HCC often             occurs in a hypoxic environment and hypoxia can activate metastatic programs,             ultimately leading to tumor recurrence or metastasis. Thus, the discovery and             subsequent development of novel agents to block HCC invasion and migration are             the primary objectives of hepatic cancer research. The Notch1 signaling pathway             might be involved in hypoxia-induced carcinoma metastasis. However, the mechanisms             by which Notch1 mediates cell metastasis, particularly in hepatocellular carcinoma,             are not yet entirely clear. The results of the present study show that hypoxia             increases the invasion and migration capacities of different HCC cells. Activation             of the Notch1 signaling pathway contributes to hypoxia-induced invasion and migration             in HCC cells. The activated Notch1 signaling pathway can regulate Snail/E-cadherin             through cyclooxygenase-2 (COX-2) under hypoxic conditions. The above results suggest             that the Notch1/COX-2/Snail/E-cadherin pathway is possibly associated with hypoxia-induced             invasion and migration in HCC cells. Thus, targeting Notch1 may be useful for             devising novel preventive and therapeutic strategies for HCC.
authors.affiliation: Department of Hepatobiliary Surgery, 302 Hospital of PLA, Beijing 100039, PR China.
authors.forename: Ling-Xiang
authors.initials: LX
authors.lastname: Yu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Li
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Wang
authors.forename: Shao-Geng
authors.initials: SG
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human