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Volume 3, Issue 4
J Clin Epigenet
ISSN: 2472-1158
Epigenetics 2017
November 06-08, 2017
EPIGENETICS & CHROMATIN
November 06-08, 2017 | Frankfurt, Germany
2
nd
International Congress on
J Clin Epigenet 2017, 3:4
DOI: 10.21767/2472-1158-C1-003
SOX18 transcription factor interactome: Protein-protein interaction a new road for anti-cancer drug
discovery SOX18 transcription factor interactome: Protein-protein interaction a new road for anti-
cancer drug discovery
Mehdi Moustaqil
1
EMBL, Australia
2
Single Molecule Science-UNSW, Australia
P
harmacological targeting of transcription factors holds great promise for the development of new therapeutics, but the
strategies based on blockading DNA binding, nuclear shuttling, or individual protein partner recruitment have had
limited success to date. A single transcription factor has multiple transcriptional effects that are context-dependent. This
versatility of activity is thought to be mediated by different protein-protein interactions (PPIs). Therefore, these PPIs offer
a new avenue for the selective pharmacological modulation of transcription factor activity, which will lead to develop novel
therapeutics. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically
inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods
to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular
development and thus cancer metastasis. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-
dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs
in vitro
and interfered with
vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor
significantly improved survival by reducing tumor vascular density and metastatic spread.