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

• Published in: FEBS letters Vol. 587; no. 14; pp. 2105 - 2111
• Main Authors: Qinyu, Li, Long, Cui, Zhen-dong, Du, Min-min, Shi, Wei-ze, Wu, Wei-ping, Yang, Cheng-hong, Peng
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 11.07.2013
• Subjects: Acetylation; Binding Sites; C-myc; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; FOXO6; Gastric cancer; Hepatocyte Nuclear Factor 4 - metabolism; Histone Deacetylases - metabolism; Histones - metabolism; HNF4; Humans; Promoter Regions, Genetic; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Stomach Neoplasms; Transcription, Genetic; Transcriptional Activation; Up-Regulation; Cell proliferation; FOXO6; C-myc; HNF4; Gastric cancer
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.05.027

•FOXO6 is upregulated in gastric cancer tissues.•FOXO6 regulates cell proliferation in gastric cancer cells.•FOXO6 overexpression induces C-myc transcription in gastric cancer cells.•FOXO6 upregulates C-myc promoter activity through an HNF4 binding site.•FOXO6 cooperates with HNF4 to transactivate C-myc expression. 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. FOXO6physically interacts with HNF4 by anti bait coimmunoprecipitation (View Interaction: 1, 2)