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Review
. 2004 Apr 1;91(5):896-903.
doi: 10.1002/jcb.20012.

Ets proteins in biological control and cancer

Tien Hsu  1 , Maria Trojanowska, Dennis K Watson
Affiliations
Review

Ets proteins in biological control and cancer

Tien Hsu et al. J Cell Biochem. .

Abstract

The Ets family consists of a large number of evolutionarily conserved transcription factors, many of which have been implicated in tumor progression. Extensive studies on this family of proteins have focused so far mainly on the biochemical properties and cellular functions of individual factors. Since most of the Ets factors can bind to the core consensus DNA sequence GGAA/T in vitro, it has been a challenge to differentiate redundant from specific functions of various Ets proteins in vivo. Recent findings, however, suggest that such apparent redundancy may in fact be a central component of a network of differentially regulated specific Ets factors, resulting in distinct biological and pathological consequences. The programmed "Ets conversion" appears to play a critical role during tumor progression, especially in control of cellular changes during epithelial-mesenchymal transition and metastasis. Coordination of multiple Ets gene functions also mediates interactions between tumor and stromal cells. As such, these new insights may provide a novel view of the Ets gene family as well as a focal point for studying the complex biological control involved in tumor progression.

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Figures

Fig. 1
Fig. 1
Ets conversion in EMT. Selected examples of Ets factors and target genes are used to illustrate the Ets conversion model during EMT. A: The epithelial and stromal (fibroblasts, ECM, and endothelium) compartments are shown for normal and invasive tissues. Ets targets that are expressed at high levels in normal epithelium are shown in blue. They are down-regulated in the invasive tumor cells. In the invasive phase, several up-regulated Ets target genes are shown in red and in their respective compartments. Tumor-induced neo-vasculature is shown in red. VEGF signaling, emanating from both tumor cells and fibroblasts, is provided as an example for tumor–stroma interaction and feed-back regulatory loop mediated by Ets. B: Examples of different Ets factors that are involved in the Ets conversion program during EMT within different cellular compartments. Arrow direction indicates up-regulation ( formula image) or down-regulation ( formula image) in invasive cancer. C: Examples of target genes differentially regulated by the indicated Ets factors as a result of Ets conversion in different cellular compartments. Abbreviations: BM, basement membrane; Col I, collagen I; E-cad, E-cadherin; ECM, extracellular matrix; EMT, epithelial–mesenchymal transition; MMP, matrix metalloproteinase; TN-C, tenascin C; uPA, urokinase-like plasminogen activator.
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