FOXO6 promotes gastric cancer cell tumorigenicity via upregulation of C-myc.

The aberrant regulation of many related genes is involved in the development and progression of gastric carcinoma. In the present study, we show that mRNA and protein levels of FOXO6 are upregulated in gastric cancer tissues. Forced overexpression of FOXO6 promotes gastric cancer cell proliferation, while knockdown of FOXO6 expression inhibits proliferation. We show that ectopic FOXO6 expression induces the expression of C-myc. Furthermore, we found that FOXO6 physically interacts with the transcription factor hepatic nuclear factor 4 (HNF4) in gastric cancer cells. FOXO6 induces C-myc expression by associating to HNF4 and mediating histone acetylation, and the dissociation of HDAC3 from the promoter of the C-myc gene. Therefore, our results suggest a previously unknown FOXO6/HNF4/C-myc molecular network controlling gastric cancer development.