title: Targeted Inhibition of Snail Activity in Breast Cancer Cells by Using a Co(III) -Ebox Conjugate.
abstract: 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. Co(III) -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 Co(III) -Ebox in inhibiting the invasive aspects of heregulin-β1(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.
authors: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, Radiology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA.
authors: Luke F
authors: LF
authors: Vistain
authors: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, Radiology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA.
authors: Natsuho
authors: N
authors: Yamamoto
authors: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, Radiology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA.
authors: Richa
authors: R
authors: Rathore
authors: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, Radiology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA.
authors: Peter
authors: P
authors: Cha
authors: Department of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, Radiology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA. tmeade@northwestern.edu.
authors: Thomas J
authors: TJ
authors: Meade
mesh_terms: D001483:Base Sequence; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D020890:Neuregulin-1 / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D056831:Coordination Complexes; D020890:Neuregulin-1; D009841:Oligonucleotides; D014157:Transcription Factors; C087230:heregulin beta1; D003035:Cobalt
keywords: Snail; cancer; cobalt; metastasis; transcription factor