Abstract 4591: Overexpression of p62/IMP2 can promote cell migration in hepatocellular carcinoma (HCC) via activating Wnt/ β-catenin pathway

Abstract

Abstract There are three members in the family of insulin-like growth factor 2 mRNA binding proteins (IMP): IMP1, IMP2 and IMP3. The IMPs are oncofetal proteins, expressed during embryogenesis and lost in most tissues in adults. However, IMPs were found overexpressed in various cancers. IMPs share similar protein structure in mammals and have similar functions: to bind specific mRNAs, regulate their expression, transportation, and degradation. Although p62/IMP2 was first reported as a tumor-associated antigen in HCC around 20 years ago, we still know little about the role of p62/IMP2 in HCC progression. Our previous studies found that p62/IMP2 was not only overexpressed in HCC tissues, but also overexpressed in HCC cell lines. To explore the biological roles of p62/IMP2 in HCC progression, p62/IMP2 was knockout in two p62/IMP2 positive HCC cell lines (SNU449, HepG2). Due to the low expression level of p62/IMP2 in SNU449, we performed the transfection experiment to overexpress p62/IMP2 in this cell line. The Wound healing assay and transwell migration assay indicated that overexpressed p62/IMP2 in both cell lines showed the ability that could promote the cell migration significantly (p<0.05). On the contrary, the lack of p62/IMP2 expression can reduce the cell migration ability (P<0.05). After analyzing the HCC expression data from Gene Expression Omnibus (GEO), the high and low IMP2 expression groups were set up based on the median expression of p62/IMP2 from GSE 14520. Three genes were selected in differential gene expression analysis with a cancer-metastasis related gene profile, including CTNNB1, ACTR2, VASP (LogFC > 0.3, Adj. p<0.001). Then we performed a western blotting analysis to explore the effect of overexpressed p62/IMP2 on Wnt/β-catenin pathway-related proteins. Overexpressed p62/IMP2 significantly enhance the expression of Wnt and β-catenin, whereas inhibiting the expression of Gsk3b and E-cadherin. Moreover, the migration ability of SNU449 and HepG2 cells were significantly reduced (p<0.05) after cultured with 10mM Wnt/β-catenin signaling pathway inhibitor XAV939 for 24h. In summary, our data showed that overexpressed p62/IMP2 can enhance the migration ability of HCC cells via activating Wnt/β-catenin signaling pathway. Citation Format: Mengtao Xing, Jianxiang Shi, Pei Li, Jiejie Qin, Xiaojun Zhang, Yangcheng Ma, Xiao Wang, Giulio Francia, Jianying Zhang. Overexpression of p62/IMP2 can promote cell migration in hepatocellular carcinoma (HCC) via activating Wnt/ β-catenin pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4591.