title: FOXO6 promotes gastric cancer cell tumorigenicity via upregulation of C-myc.
abstract: 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.
authors.affiliation: Shanghai Institute of Digestive Surgery, Shanghai Jiaotong University School of Medicine, Shanghai, China. rjqinyuli@gmail.com
authors.forename: Li
authors.initials: L
authors.lastname: Qinyu
authors.forename: Cui
authors.initials: C
authors.lastname: Long
authors.forename: Du
authors.initials: D
authors.lastname: Zhen-dong
authors.forename: Shi
authors.initials: S
authors.lastname: Min-min
authors.forename: Wu
authors.initials: W
authors.lastname: Wei-ze
authors.forename: Yang
authors.initials: Y
authors.lastname: Wei-ping
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng-hong
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation; D000099186:Histone Deacetylase 3
chemical_list: D051858:Forkhead Transcription Factors; D051557:Hepatocyte Nuclear Factor 4; D006655:Histone Deacetylases; D006657:Histones; D016271:Proto-Oncogene Proteins c-myc; D000099186:Histone Deacetylase 3; C478770:FOXO6 protein, human; C489427:MYC protein, human