Article

Function of the zinc-finger transcription factor SNAI2 in cancer and development

Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Annual Review of Genetics (Impact Factor: 18.12). 02/2007; 41:41-61. DOI: 10.1146/annurev.genet.41.110306.130146
Source: PubMed

ABSTRACT Elucidation of the molecular mechanisms that underlie disease development is still a tremendous challenge for basic science, and a prerequisite to the development of new and disease-specific targeted therapies. This review focuses on the function of SNAI2, a member of the Snail family of zinc-finger transcription factors, and discusses its possible role in disease development. SNAI2 has been implicated in diseases of melanocyte development and cancer in humans. Many malignancies arise from a rare population of cells that alone have the ability to self-renew and sustain the tumor (i.e., cancer stem cells). SNAI2 controls key aspects of stem cell function in mouse and human, suggesting that similar mechanisms control normal development and cancer stem cell properties. These insights are expected to contribute significantly to the genetics of cancer and to the development of both cancer therapy and new methods for assessing treatment efficacy.

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    • "Several of these activated targets have established roles as oncogenes in other cellular contexts. In contrast, genes directly repressed by EWS-FLI1 include the known tumor suppressors ERRFI1 (Duncan et al., 2010), CABLES1 (Arnason et al., 2013), IER3 (Sebens Mü erkö ster et al., 2008), and TGFBI (Wang et al., 2012) as well as mesenchymal lineage factors such as SNAI2 (Cobaleda et al., 2007), TRPS1 (Zhang et al., 2012), and CD73 (Chamberlain et al., 2007) (Tables S3 and S4). "
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    • "Snail belongs to the Snail superfamily of zinc finger transcription factors [10]. Snail and Slug, a related superfamily member, are expressed in the early mesoderm and neural crest during development [11] [12] [13]. These two zinc finger transcription factors repress E-cadherin transcription through an interaction of their C-terminal region with a 5 0 -CACCTG-3 0 sequence (referred as E-box) in the cadherin promoter [14] [15]. "
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    • "SNAI2 regulates the DCTN5 gene promoter (Fig. 5) that contains E2-box sequences (CAGGTG/CACCTG), the classical binding site of SNAI2 [13] [14] [15] [16]. We evaluated DCTN5 levels in the SNAI2 knocked down cells; we found that DCTN5 mRNA and protein levels are increased significantly in these cells (Fig. 3 and Fig. 4). "
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