Targeted Inhibition of Snail Activity in Breast Cancer Cells by Using a CoIII‐Ebox Conjugate

Publisher: John Wiley & Sons Inc

E-ISSN: 1439-7633|16|14|2065-2072

ISSN: 1439-4227

Source: CHEMBIOCHEM, Vol.16, Iss.14, 2015-09, pp. : 2065-2072

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Abstract

AbstractThe transition from a non‐invasive to an invasive phenotype is an essential step in tumor metastasis. The Snail family of transcription factors (TFs) is known to play a significant role in this transition. These TFs are zinc fingers that bind to the CAGGTG Ebox consensus sequence. CoIII‐Ebox is a cobalt(III) complex attached to an Ebox oligonucleotide that confers specificity towards Snail TFs. CoIII‐Ebox has been shown to inhibit Snail‐mediated embryonic neural crest development in Xenopus laevis, but its efficacy in inhibiting Snail‐induced cancer cell invasiveness has not been explored. Here, we describe the efficacy of CoIII‐Ebox in inhibiting the invasive aspects of heregulin‐β1(HRG)‐treated breast cancer cells. CoIII‐Ebox was found to inhibit the capacity of Snail to repress target genes after HRG induction. Snail inhibition by CoIII‐Ebox reduced the invasive propensity of cells in 2D and 3D, thereby demonstrating promise in inhibiting metastasis.