The Snail genes as inducers of cell movement and survival: implications in development and cancer

Abstract

The functions of the Snail family of zinc-finger transcription factors are essential during embryonic development. One of their best-known functions is to induce epithelial to mesenchymal transitions (EMTs), which convert epithelial cells into migratory mesenchymal cells. In recent years, many orthologues of the Snail family have been identified throughout the animal kingdom, and their study is providing new clues about the EMTdependent and -independent functions of Snail proteins. Here, we discuss these functions and how they influence cell behaviour during development and during diseases such as metastatic cancer. From these findings, we propose that Snail genes act primarily as survival factors and inducers of cell movement, rather than as inducers of EMT or cell fate. Summary

HIF‐1α regulates EMT via the Snail and β‐catenin pathways in paraquat poisoning‐induced early pulmonary fibrosis

“…Reports have shown that Snail plays an important role in the initiation of EMT 49, 50. Some studies have demonstrated that β‐catenin may be involved in the formation of pulmonary fibrosis by driving A549 cells to fibroblasts 51, 52.…”

In vivo binding to and functional repression of the VDR gene promoter by SLUG in human breast cells

“…The DNA binding domain has five C 2 H 2 type zinc fingers, which are essential for the interaction of this repressor protein with the E2-box sequences (CAGGTG/CACCTG) at the promoters of SLUGtarget genes [4][5][6]. The repressor domain consists of two distinct motifs: (i) the SNAG motif, which is conserved in many other proteins including other SNAI family members, Gfi1 and Gfi2, and ZEB1 and ZEB2 [4][5][6] and (ii) the P-motif, which we found through mutational analyses as essential for the repressor function of human SLUG (Bailey, C.K. and Chaudhuri, G., unpublished data).…”

“…These data suggests that SLUG binds to the E2-box sequences of the VDR gene promoter and recruits CtBP1 and HDAC1, which results in the inhibition of VDR gene expression by chromatin remodeling. SLUG is a member of the SNAI family of C 2 H 2 -zinc finger family of transcriptional repressors [4][5][6]. It is involved in the epithelial-mesenchymal transition during development [5], acts as an inhibitor of apoptosis [7], and causes tubulogenesis during breast and kidney developments [4,5].…”

“…SLUG is a member of the SNAI family of C 2 H 2 -zinc finger family of transcriptional repressors [4][5][6]. It is involved in the epithelial-mesenchymal transition during development [5], acts as an inhibitor of apoptosis [7], and causes tubulogenesis during breast and kidney developments [4,5]. The genes inhibited by SLUG include E-cadherin [8], claudins [9], BRCA2 [10], and cytokeratins [11].…”

Neuron-Specific Expression of Scratch Genes during Early Zebrafish Development

“…The Scratch (Scrt) family is a member of the Snail superfamily of zinc finger transcription factors which are involved in regulating cell movement processes both during embryonic development and tumor progression (Barrallo-Gimeno and Nieto, 2005;Nieto, 2002). Like the Snail family proteins, the Scrt family contains one N-terminal basic amino acid-rich domain (SNAG), which is present only in vertebrates, and five zinc finger motifs acting as sequence-specific DNA-binding motifs.…”