To date, cancer remains the number one killer disease in the western world. While several cancer therapies target tumor growth, cancer lethality is mainly due to formation of metastasis. Lymphatic vasculature plays a key role in metastasis progression, making lymphangiogenesis a promising target for therapy development. A number of transcription factors involved in lymphangiogenesis have indeed been found to be upregulated during metastasis. In this study, we focused on SOX18, a key player transcription factor in embryonic lymphatic vasculature formation.  

However, transcription factors do not work alone, they recruit intermediary proteins such as cofactors to modulate transcription. Our approach is to determine which complexes formed by transcription factors are fundamental features of gene regulation. To this end, we define the interactome of SOX18 using a platform based on the cell-free expression system for the rapid access to protein and an Alpha Screen assay to detect protein-protein interaction. Our study comprehensively maps the network of interactions, not only around SOX18, but between 25 cofactors.

Going beyond pairwise interactions allows the study of transcription factor complexes, and provides new insights into the molecular mechanisms of gene regulation. Finally, this work identifies key protein-protein interactions that could be pharmacologically targeted to suppress cancer progression.