Snail and Slug, key regulators of TGF-β-induced EMT, are sufficient for the induction of single-cell invasion

• Snail or Slug expression in H-Ras transformed MCF10AT induced an EMT-like phenotype.
• Slug or Snail expression in H-Ras transformed MCF10AT promoted invasion in vitro.
• This led to invasion and metastasis in an embryonic zebrafish xenograft model.
• This links TGF-β-induced EMT to single cell invasion and metastasis in zebrafish.

TGF-β plays a dual role in cancer; in early stages it inhibits tumor growth, whereas later it promotes invasion and metastasis. TGF-β is thought to be pro-invasive by inducing epithelial-to-mesenchymal transition (EMT) via induction of transcriptional repressors, including Slug and Snail.In this study, we investigated the role of Snail and Slug in TGF-β-induced invasion in an in vitro invasion assay and in an embryonic zebrafish xenograft model. Ectopic expression of Slug or Snail promoted invasion of single, rounded amoeboid cells in vitro. In an embryonic zebrafish xenograft model, forced expression of Slug and Snail promoted single cell invasion and metastasis. Slug and Snail are sufficient for the induction of single-cell invasion in an in vitro invasion assay and in an embryonic zebrafish xenograft model.