DP103-GSK3β-WNT CASCADE PROMOTES WNT/β-CATENIN SIGNALING IN PARENTAL AND STEM CELLS FROM TRIPLE NEGATIVE BREAST CANCER

Abstract

Breast cancer is a principal cause of death in women globally. Despite recent advances in breast cancer therapeutics, mortality of metastatic triple negative breast cancer (TNBC) subtype remains high due to the lack of targeted therapy. DEAD box RNA helicase DP103 was identified as a novel prognostic biomarker and metastasis-driving oncogene, highly expressed in TNBC subtype. Increased DP103 expression was also associated with increased Wnt responsiveness in TNBC cells, which led to the investigation of DP103's association with the Wnt/β-catenin signalling pathway. Preliminary clinical, in vivo and in vitro data have revealed DP103 to play a novel role as a positive modulator of the Wnt/β-catenin signalling pathway in TNBCs. DP103 was also identified to be a novel Wnt target gene, further activating the pathway through a positive feedback loop. Our data have presented DP103 as an attractive option for molecular directed therapy in TNBC patients, breaking the Achilles’ heel of this positive feedback loop.