Journal
CHEMBIOCHEM
Volume 16, Issue 14, Pages 2065-2072Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201500289
Keywords
cancer; cobalt; metastasis; Snail; transcription factor
Funding
- National Cancer Institute [RO3A167715]
- National Institute for Arthritis and Musculoskeletal and Skin Diseases (NIAMSD) [P30AR057216]
- National Science Foundation [CHE-9810378/005]
- National Institutes of Health Centers of Cancer Nanotechnology Excellence initiative of the National Cancer Institute [U54A119341]
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The 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. Co-III-Ebox is a cobalt(III) complex attached to an Ebox oligonucleotide that confers specificity towards Snail TFs. CoIII-Ebox has been shown to inhibit Snailmediated 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 Co-III-Ebox in inhibiting the invasive aspects of heregulin-beta 1(HRG)-treated breast cancer cells. Co-III-Ebox was found to inhibit the capacity of Snail to repress target genes after HRG induction. Snail inhibition by Co-III-Ebox reduced the invasive propensity of cells in 2D and 3D, thereby demonstrating promise in inhibiting metastasis.
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