Opposing Roles of the Forkhead Box Factors FoxM1 and FoxA2 in Liver Cancer.

ABSTRACT: The forkhead box transcription factor FoxM1 is essential for hepatocellular carcinoma (HCC) development, and its overexpression coincides with poor prognosis. Here, we show that the mechanisms by which FoxM1 drives HCC progression involve overcoming the inhibitory effects of the liver differentiation gene FoxA2. First, the expression patterns of FoxM1 and FoxA2 in human HCC are opposite. We show that FoxM1 represses expression of FoxA2 in G₁ phase. Repression of FoxA2 in G₁ phase is important, as it is capable of inhibiting expression of the pluripotency genes that are expressed mainly in S-G₂ phases. Using a transgenic mouse model for oncogenic Ras-driven HCC, we provide genetic evidence for a repression of FoxA2 by FoxM1. Conversely, FoxA2 inhibits expres

SUBMITTER: Chand V 

PROVIDER: S-EPMC6497570 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature