Proliferation and migration of hepatoblastoma cells are mediated by IRS-4 via PI3K/Akt pathways.

Levels of IRS-4 (insulin receptor substrate-4) in hepatoblastoma cells from the patients, HepG2 and HuH-6 cell lines were measured by Western Blot analysis, and they were all found significantly higher than those of normal hepatic cells. When the HepG2 and HuH-6 cells cultivated in vitro were treated with IRS-4 and infected with recombinant adenovirus containing IRS-4 gene, the proliferation and migration of the cells were significantly improved. Meanwhile, the expressions of PI3K (phosphatidylinositol 3'-kinase), pS473 Akt (Protein Kinase B) and pThr308 Akt were positively regulated by IRS-4 overexpression. These results indicated that IRS-4 was very likely to be involved in PI3K/Akt path way, which was further confirmed by the fact that the PI3K/Akt blocker LY294002 attenuated the proliferation and migration of the hepatoblastoma cells. In conclusion, IRS-4 enhanced the proliferation and migration of the hepatoblastoma cells via PI3K/Akt pathways.