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Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in Drosophila
Author(s) -
Pallavi S K,
Ho Diana M,
Hicks Chindo,
Miele Lucio,
ArtavanisTsakonas Spyros
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.129
Subject(s) - biology , drosophila (subgenus) , signal transduction , microbiology and biotechnology , cancer research , notch signaling pathway , drosophila melanogaster , genetics , gene
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.