INTERPLAY BETWEEN MEVALONATE AND HIPPO PATHWAYS REGULATES DDX20 TRANSCIPTION VIA YAO-TEAD COMPLEX IN TRIPLE NEGATIVE BREAST CANCERS

Abstract

Statins, inhibit HMGCR of the mevalonate pathway and was found to associate with a reduced breast cancer risk. However, few studies utilised biomarkers to obtain consistent outcomes. We investigated DDX20 as a surrogate marker for statin response in breast cancers. We assessed correlation between mevalonate pathway genes and DDX20 in breast tumors and breast cancer cells were treated with simvastatin to assess the alteration in DDX20 expression. In the mouse model and clinical trials, simvastatin was administered and IHC staining of DDX20 was performed. Our results demonstrate that triple negative breast cancer with high DDX20 is more sensitive to simvastatin. Exposure of TNBC cells to statins decreases DDX20 expression via RhoA. Similar activity was observed in tumor biopsies in mice and breast cancer patients. As another study reported the mevalonate pathway regulates YAP via RhoA, we have uncovered an interplay between DDX20 and YAP-TEAD complex.