The Notch1/cyclooxygenase-2/Snail/E-cadherin pathway is associated with hypoxia-induced hepatocellular carcinoma cell invasion and migration

Yu,Ling-Xiang; Zhou,Liang; Li,Mo; Li,Zhi-Wei; Wang,De-Sheng; Zhang,Shao-Geng

doi:10.3892/or.2012.2103

The Notch1/cyclooxygenase-2/Snail/E-cadherin pathway is associated with hypoxia-induced hepatocellular carcinoma cell invasion and migration

Authors:
- Ling-Xiang Yu
- Liang Zhou
- Mo Li
- Zhi-Wei Li
- De-Sheng Wang
- Shao-Geng Zhang
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Affiliations: Department of Hepatobiliary Surgery, 302 Hospital of PLA, Beijing 100039, P.R. China, Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. Chin
Published online on: October 23, 2012 https://doi.org/10.3892/or.2012.2103
Pages: 362-370

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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.

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