AP-2 alpha inhibits hepatocellular carcinoma cell growth and migration

作者：Huang, Wenhuan; Chen, Cheng; Liang, Zhongheng; Qiu, Junlu; Li, Xinxin; Hu, Xiang; Xiang, Shuanglin; Ding, Xiaofeng^*; Zhang, Jian^*

来源：International Journal of Oncology, 2016, 48(3): 1125-1134.

DOI：10.3892/ijo.2016.3318

• AP-2 alpha
• hepatocellular carcinoma
• cellular growth and migration
• lentiviral overexpression system
• extracellular signal-regulated protein kinase
• p53
• cisplatin
• epithelial-to-mesenchymal transition
• E-cadherin
• vimentin
• MMP-9
• beta-catenin

Transcription factor AP-2 alpha is involved in many types of human cancers, but its role in hepatocellular carcinogenesis is largely unknown. In this study, we found that expression of AP-2 alpha was low in 40% of human hepatocellular cancers compared with adjacent normal tissues by immunohistochemical analysis. Moreover, AP-2 alpha expression was low or absent in hepatocellular cancer cell lines (HepG2, Hep3B, SMMC-7721 and MHHC 97-H). Human liver cancer cell lines SMMC-7721 and Hep3B stably overexpressing AP-2 alpha were established by lentiviral infection and puromycin screening, and the ectopic expression of AP-2 alpha was able to inhibit hepatocellular cancer cell growth and proliferation by cell viability, MTT assay and liquid colony formation in vitro and in vivo. Furthermore, AP-2 alpha overexpression decreased liver cancer cell migration and invasion as assessed by wound healing and Transwell assays, increasing the sensitivity of liver cancer cells to cisplatin analyzed by MTT assays. Also AP-2 alpha overexpression suppressed the sphere formation and renewed the ability of cancer stem cells. Finally, we found that AP-2 alpha is epigenetically modified and modulates the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), beta-catenin, p53, EMT, and CD133 expression in liver cancer cell lines. These results suggested that AP-2 alpha expression is low in human hepatocellular cancers by regulating multiple signaling to affect hepatocellular cancer cell growth and migration. Therefore, AP-2 alpha might represent a novel potential target in human hepatocellular cancer therapy.

• 出版日期2016-3
• 单位湖南师范大学