The transcription factor Ets21C drives tumor growth by cooperating with AP-1

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

The scribble-Dlg-Lgl module in cell polarity regulation

Although the Scribble polarity module has long been known as a key regulator of apicobasal polarity, it is only recently that its broader role in the control of near all polarity states and transitions is being appreciated. Here we review the Scribble module in the regulation of cell polarity and other cellular functions at the molecular and cellular level. The more recent detailed analysis of multiple vertebrate models for each of its component homologues, Scribble, Dlg and Lgl, has revealed specific but also common roles for individual homologues in a variety of developmental contexts. In addition, emerging data has also implicated the Scribble polarity module in human developmental syndromes and the etiology of human cancer, highlighting a need for a better understanding of this polarity module for therapeutic purposes. Unlocking the temporal and spatial coordination of the myriad interactions that these signaling scaffolds regulate is a major challenge for the field and will be key to resolve the function of Scribble, Dlg, and Lgl in the control of cell polarity and tissue architecture