Biology

Dr Madhura Kulkarni
Cancer Science Institute of Singapore, Centre for Translational Medicine, Singapore

YAP is a co-activator protein and downstream effector of Hippo tumor suppressor pathway. It has emerged as an important oncoprotein in solid tumor progression. We have identified antagonistic interaction between RUNX1/RUNX3 transcription factors and YAP. RUNX transcription factors abrogate YAP-mediated pro-tumorigenic properties of mammary epithelial cell lines in an interaction dependent manner. Whole genome expression profiling of available breast cancer patients for YAP and RUNX1/RUNX3 revealed similar antagonistic association towards patient survival outcomes, confirming clinical significance of YAP-RUNX interplay. Tumor microarray on breast cancer patient samples was done to confirm this antagonistic clinical association. YAP-RUNX antagonistic interplay and its association with patient survival outcomes can be a prognostic tool to predict clinical outcomes of breast cancer patients. Further to this study, we identified high YAP expression significantly contributes to EMT, stem-ness and angiogenesis properties of a specific molecular subtype of breast cancer, TNBC. TNBC is the most recurrent subtype amongst all the breast cancer subtypes. Our study highlights a strong link between elevated YAP expression and tumor recurrence in TNBC. Stratification of YAP expression in TNBC tumors can serve as a novel molecular signature to identify worse prognostic subset of TNBC with significant clinical implications.