Hepatocellular carcinoma (HCC) is one of the most common type of cancer and the third leading cause of cancer related death in worldwide. Insulin-like growth factor 2 mRNA binding protein 2 (p62/IMP2/IGF2BP2) was originally reported as an autoantigen in HCC which belongs to IMPs family. The IMPs family contains three members: IMP1, IMP2 and IMP3, which share similar protein structure. IMPs are oncofetal proteins, which are expressed during embryogenesis and lost in most tissues in adults. Therefore, p62/IMP2 can be used as a potential biomarker for early diagnosis of HCC. We have evaluated the expression of p62/IMP2 protein both in human tissues and HCC cell lines by immunohistochemistry and western blotting analysis, and found that p62/IMP2 protein is overexpressed in human HCC tissues compared with normal human liver tissues (score= 10.30, n=40 vs. score =5.23, n=30, p<0.05). The expression of p62/IMP2 was scored by immune-staining intensity and positively immune-staining cell numbers. At the same time, we found that p62/IMP2 was also overexpressed in several HCC cell lines. Stable p62/IMP2 overexpression and depletion SNU449 human HCC cell line was made by using p62/IMP2 cDNA transfection and lentivirus mediated knockdown approaches, and it was further confirmed by western blotting analysis. Wound healing assay has shown that overexpression of p62/IMP2 can significantly enhance the cell migration ability in SNU449 cells. On the contrary, the depletion of p62/IMP2 can reduce the migration ability in SNU449 cells (p<0.05). Moreover,MTT assay has also shown p62/IMP2 overexpressed cells may have a higher rate of proliferation at 72h(p<0.05). In addition, we have observed that overexpression of p62/IMP2 can significant inhibit the expression of E-cadherin in western blotting analysis. In summary, our data would suggest that overexpression p62/IMP2 may promote metastasis via inhibition of E-cadherin expression in HCC.

Citation Format: Mengtao Xing, Pei Li, Jitian Li, Jianxiang shi, Liping Dai, Giulio Francia, Jianying Zhang. Overexpression of P62/IMP2 promotes metastasis in hepatocellular carcinoma via inhibition of E-cadherin expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4850. doi:10.1158/1538-7445.AM2017-4850