Understanding how RSKs regulate transcription factors in triple negative breast cancer

There is a current gap in therapeutic approaches towards triple negative breast cancer (TNBC) and unlike other breast cancer subtypes, it lacks a recommended chemotherapy treatment. It is therefore essential to better characterise the signalling pathways that drive tumour growth to identify novel therapeutic methods.

I will characterise a novel drug target, the p90 ribosomal protein S6 kinase (RSKs) family. This family consists of four human isoforms (RSK1-4), which are multifunctional effectors of the ERK/MAPK signalling cascade. In cancer, RSK isoforms perform non-redundant functions and, more precisely, in TNBC RSK1/2 promote tumour metastasis, while RSK4 is a tumour suppressor protein. These opposite roles are linked to the ability of RSKs to differentially modulate gene expression by directly regulating transcription factors (TFs) activity. However, the mechanism that allows RSKs to recognise and modulate the activity of different TFs and initiate different signalling pathways, is still unclear. The aim of this project is to understand which RSK regulates which TF using a combination of biophysical, enzymatic and cellular studies.

The findings of this study will improve understanding of cell signalling and cell survival, which will form a foundation for the design of more specific inhibitors.