title: The transcription factor Ets21C drives tumor growth by cooperating with AP-1.
abstract: Tumorigenesis is driven by genetic alterations that perturb the signaling networks regulating proliferation or cell death. In order to block tumor growth, one has to precisely know how these signaling pathways function and interplay. Here, we identified the transcription factor Ets21C as a pivotal regulator of tumor growth and propose a new model of how Ets21C could affect this process. We demonstrate that a depletion of Ets21C strongly suppressed tumor growth while ectopic expression of Ets21C further increased tumor size. We confirm that Ets21C expression is regulated by the JNK pathway and show that Ets21C acts via a positive feed-forward mechanism to induce a specific set of target genes that is critical for tumor growth. These genes are known downstream targets of the JNK pathway and we demonstrate that their expression not only depends on the transcription factor AP-1, but also on Ets21C suggesting a cooperative transcriptional activation mechanism. Taken together we show that Ets21C is a crucial player in regulating the transcriptional program of the JNK pathway and enhances our understanding of the mechanisms that govern neoplastic growth.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Janine
authors.initials: J
authors.lastname: Toggweiler
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Willecke
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Konrad
authors.initials: K
authors.lastname: Basler
mesh_terms: D000818:Animals; D001665:Binding Sites; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D047368:Tumor Burden
chemical_list: D029721:Drosophila Proteins; C000608103:Ets21C protein, Drosophila; D050783:Proto-Oncogene Proteins c-ets; D018808:Transcription Factor AP-1