title: Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in Drosophila.
abstract: Genetic analyses in Drosophila revealed a synergy between Notch and the pleiotropic transcription factor Mef2 (myocyte enhancer factor 2), which profoundly influences proliferation and metastasis. We show that these hyperproliferative and invasive Drosophila phenotypes are attributed to upregulation of eiger, a member of the tumour necrosis factor superfamily of ligands, and the consequent activation of Jun N-terminal kinase signalling, which in turn triggers the expression of the invasive marker MMP1. Expression studies in human breast tumour samples demonstrate correlation between Notch and Mef2 paralogues and support the notion that Notch-MEF2 synergy may be significant for modulating human mammary oncogenesis.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Pallavi
authors.forename: Diana M
authors.initials: DM
authors.lastname: Ho
authors.forename: Chindo
authors.initials: C
authors.lastname: Hicks
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Spyros
authors.initials: S
authors.lastname: Artavanis-Tsakonas
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D064326:MEF2 Transcription Factors; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis; D018006:Myogenic Regulatory Factors / Q000378:metabolism / Q000502:physiology*; D009362:Neoplasm Metastasis; D051880:Receptors, Notch / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D029721:Drosophila Proteins; D064326:MEF2 Transcription Factors; C499409:Mef2 protein, Drosophila; D008565:Membrane Proteins; D018006:Myogenic Regulatory Factors; C497759:N protein, Drosophila; D051880:Receptors, Notch; C464573:egr protein, Drosophila; D020781:Matrix Metalloproteinase 1