SNAI1: a key regulator of epithelial-to-mesenchymal transition (EMT)

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In this image of the month, we focus on the transcription factor SNAI1, one of the major drivers of EMT. EMT is the cellular process during which epithelial cells loosen their connections with neighboring cells and modify their interactions with the extracellular matrix, thus acquiring mesenchymal traits and a more motile phenotype. EMT is crucial for the formation of tissues and organs during embryogenesis, however in the disease context, the same process is also associated with fibrosis, cancer progression and metastasis (Nieto et al, 2016 ).

SNAI1 (or SNAIL) is responsible for the transcriptional repression of genes related to the epithelial phenotype on one hand (such as the cell-to-cell adhesion protein E-cadherin), and for promoting migratory and invasive properties of cells on the other (Barrallo-Gimeno & Nieto, 2005). SNAI1 regulates gene expression by interacting with chromatin remodeling complexes, and as anticipated, it is localized in the nucleus of cells. But Snail can also localize in the cytoplasm even though its half-life is very short in this cellular compartment as it is targeted for proteasomal degradation (Baulida et al, 2019).

Interestingly, SNAI1 is more than an EMT driver: It also protects from cell death and promotes cell survival, which is essential so that embryonic migratory cells reach their final destinations. On the other hand, this resistance to cell death conferred by SNAI1 allows cancer cells to disseminate from the primary tumor and form metastasis at distant tissues (Vega et al, 2004). SNAI1 is also involved in metabolic reprogramming as well as in suppression of immune responses in cancer cells (Dong et al, 2013, Kudo-Saito et al, 2009). As high SNAI1 expression is associated with poor prognosis in various types of cancer such as breast cancer and colorectal cancer, this makes it an attractive target for the development of new therapeutic drugs.