title: AP-2α inhibits hepatocellular carcinoma cell growth and migration.
abstract: Transcription factor AP-2α 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-2α was low in 40% of human hepatocellular cancers compared with adjacent normal tissues by immunohistochemical analysis. Moreover, AP-2α 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-2α were established by lentiviral infection and puromycin screening, and the ectopic expression of AP-2α 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-2α 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-2α overexpression suppressed the sphere formation and renewed the ability of cancer stem cells. Finally, we found that AP-2α is epigenetically modified and modulates the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), β-catenin, p53, EMT, and CD133 expression in liver cancer cell lines. These results suggested that AP-2α expression is low in human hepatocellular cancers by regulating multiple signaling to affect hepatocellular cancer cell growth and migration. Therefore, AP-2α might represent a novel potential target in human hepatocellular cancer therapy.
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Wenhuan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Zhongheng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Junlu
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ding
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D016086:Lentivirus; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011691:Puromycin / Q000737:chemistry; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D050656:Transcription Factor AP-2; D011691:Puromycin; D002945:Cisplatin