title: Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness.
abstract: p53 is an established tumor suppressor that can activate the transcription of multiple target genes. Recent evidence suggests that p53 may contribute to the regulation of cell invasion and migration. In this study, we show that the forkhead box transcription factor FOXF1 is a novel target of the p53 family because FOXF1 is upregulated by p53, TAp73 and TAp63. We show that FOXF1 is induced upon DNA damage in a p53-dependent manner. Furthermore, we identified a response element located within the FOXF1 gene that is responsive to wild-type p53, TAp73β and TAp63γ. The ectopic expression of FOXF1 inhibited cancer cell invasion and migration, whereas the inactivation of FOXF1 stimulated cell invasion and migration. We also show that FOXF1 regulates the transcriptional activity of E-cadherin (CDH1) by acting on its FOXF1 consensus binding site located upstream of the E-cadherin gene. Collectively, our results show that FOXF1 is a p53 family target gene, and our data suggest that FOXF1 and p53 form a portion of a regulatory transcriptional network that appears to have an important role in cancer cell invasion and migration.
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Koyama
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: M
authors.identifier: 0000000285071726
authors.initials: M
authors.lastname: Idogawa
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tokino
mesh_terms: D015703:Antigens, CD; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D020218:Response Elements; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53