The role of MLK4 amplification in breast cancer progression – studies in 3D cell culture and in vivo models

Gene amplification is a genetic alteration that accelerates cancer progression. Numerous oncogenes have been found in the amplified regions of the genome, but many are still to be investigated towards their contribution in tumorigenesis. Recent cancer genomics data show MLK4 amplification in breast carcinoma and our initial work revealed that MLK4 knock-down in breast cancer cell lines results in decreased viability. The objective is to assess the impact of MLK4 amplification on tumor growth and metastasis. We will perform experiments in 3D cell cultures to study the formation of spheroids and we will test novel MLK inhibitors in 3D-drug response assay. Furthermore, the role of MLK4 amplification will be evaluated in mouse models. Finally, we will assess the correlation between the clinical outcome of patients and the level of MLK4. Summarising, the proposed research will contribute to the understanding of the role of MLK4 amplification in breast cancer.