title: Transcription factor HBP1 is a direct anti-cancer target of transcription factor FOXO1 in invasive oral cancer.
abstract: Either FOXO1 or HBP1 transcription factor is a downstream effector of the PI3K/Akt pathway and associated with tumorigenesis. However, the relationship between FOXO1 and HBP1 in oral cancer remains unclear. Analysis of 30 oral tumor specimens revealed that mean mRNA levels of both FOXO1 and HBP1 in non-invasive and invasive oral tumors were found to be significantly lower than that of the control tissues, and the status of low FOXO1 and HBP1 (< 0.3 fold of the control) was associated with invasiveness of oral tumors. To investigate if HBP1 is a direct transcription target of FOXO1, we searched potential FOXO1 binding sites in the HBP1 promoter using the MAPPER Search Engine, and two putative FOXO1 binding sites located in the HBP1 promoter -132 to -125 bp and -343 to -336 bp were predicted. These binding sites were then confirmed by both reporter gene assays and the in cellulo ChIP assay. In addition, Akt activity manipulated by PI3K inhibitor LY294002 or Akt mutants was shown to negatively affect FOXO1-mediated HBP1 promoter activation and gene expression. Last, the biological significance of the FOXO1-HBP1 axis in oral cancer malignancy was evaluated in cell growth, colony formation, and invasiveness. The results indicated that HBP1 knockdown potently promoted malignant phenotypes of oral cancer and the suppressive effect of FOXO1 on cell growth, colony formation, and invasion was alleviated upon HBP1 knockdown in invasive oral cancer cells. Taken together, our data provide evidence for HBP1 as a direct downstream target of FOXO1 in oral cancer malignancy.
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Chien-Yi
authors.initials: CY
authors.lastname: Chan
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, National Sun Yatsen University, Kaohsiung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Jim Jinn-Chyuan
authors.initials: JJ
authors.lastname: Sheu
authors.affiliation: GB Lifesciences, San Diego, CA, USA.
authors.forename: Mendel M
authors.initials: MM
authors.lastname: Roth
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: I-Tai
authors.initials: IT
authors.lastname: Chou
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Lien
authors.affiliation: Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Ming-Fen
authors.initials: MF
authors.lastname: Lee
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chun-Yin
authors.initials: CY
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D009055:Mouth / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C486328:HBP1 protein, human; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D051057:Proto-Oncogene Proteins c-akt
keywords: FOXO1; HBP1; oral cancer