title: The transcription factor FOXM1c binds to and transactivates the promoter of the tumor suppressor gene E-cadherin.
abstract: This study demonstrates for the first time that FOXM1c transactivates the murine E-cadherin promoter. It shows also that the purified DNA-binding domain of FOXM1c binds to the murine and human E-cadherin promoters in vitro, namely to a perfectly conserved FOXM1 site. Thus, this study identifies E-cadherin as a new direct FOXM1c target gene. This finding is surprising because E-cadherin is a tumor suppressor gene whereas FOXM1 is a proliferation-associated and tumorigenesis-promoting transcription factor. The transmembrane glycoprotein E-cadherin mediates cell-cell adhesion in adherens junctions. Its expression is frequently lost or reduced in human tumors, which correlates with poor prognosis. Downregulation of E-cadherin represents a central event in epithelial-to-mesenchymal transition. In contrast, FOXM1 contributes to oncogenic transformation and participates in tumor initiation and progression. It is overexpressed in many human cancers and a high FOXM1 level correlates with poor prognosis. FOXM1 stimulates cell proliferation and promotes cell cycle progression at the G1/S- and G2/M-transitions. The surprising finding that FOXM1c transactivates the promoter of the tumor suppressor gene E-cadherin points to a tumor-suppressive property of FOXM1. This view is supported by FOXM1's new tumor suppressor role as others reported that urethane-induced lung tumorigenesis is increased in mice with an endothelial cell-specific foxm1 deletion.
authors.affiliation: Institute of Molecular Biology, Medical School Hannover, Hannover, Germany. iwiwiwi@web.de
authors.forename: Inken
authors.initials: I
authors.lastname: Wierstra
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D016195:G2 Phase; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation
chemical_list: D015820:Cadherins; D051858:Forkhead Transcription Factors