Congratulations to Cai Wanpei, a PhD student in Dr. Alan Prem Kumar’s group, for winning the Best Poster Award at the Science on the Swan Inaugural Conference 2015. The conference was held from 21 – 23 April in the Perth Convention and Exhibition Centre, Perth, Western Australia.
Science on the Swan showcases the very best of medical science and health research in Western Australia (WA). It brings together all five of WA’s major Universities (The University of Western Australia, Curtin University, Murdoch University, Edith Cowan University and The University of Notre Dame) in partnership with the key teaching and research hospitals, the medical research institutes of WA and the WA Government through the Department of Health and the Office of Science.
RNA Helicase DP103: Targeting Wnt/β-catenin signaling in Triple Negative Breast Cancers
Wanpei Cai1,2, Gautam Sethi1,2, Arunasalam Dharmarajan5, David M. Virshup3,4, Alan Prem Kumar1,2,5,6
1Cancer Science Institute of Singapore, National University of Singapore; Departments of 2Pharmacology and 3Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore; 4Cancer & Stem Cell Biology Program, Graduate Medical School, Duke-NUS; 5School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Western Australia; 6Department of Biological Sciences, University of North Texas, Denton, TX, USA
Breast cancer is a principle cause of death in women globally and a diverse malignancy. Despite recent advances in breast cancer therapeutics, mortality of metastatic triple negative breast cancer (TNBC) subtype remains high; due to their lack hormone receptors expression for targeted therapy. Identification of new prognostic markers and therapeutic targets for this group of breast cancers is essential. Aberrant activation of Wnt/β-catenin signaling has been associated with breast cancers; where 40% of total breast cancers have elevated β-catenin levels with increased Wnt activity. Herein, we identify DEAD-box RNA helicase DP103 as a novel prognostic biomarker and metastasis-driving oncogene; highly expressed in TNBC subtype. High DP103 expressing TNBC cells correlated with increased Wnt activity, leading us to hypothesize a role of DP103 in modulating Wnt/β-catenin pathway. Furthermore depletion of DP103 in metastatic TNBC cells decreases Wnt/β-catenin activity and expression of downstream Wnt target genes while overexpression of DP103 increased Wnt activity. Depletion of DP103 also decreased phosphorylation of LRP6 and several Wnt modulators required for Wnt activation. Interestingly, induction of Wnt/β-catenin signaling in Wnt responsive TNBC cells also significantly increased DP103 expression, indicating a possible positive feedback loop. Collectively, our data suggest a novel regulatory role of DP103 in the Wnt/β-catenin signaling pathway, and presents itself as a potential drug target for inhibition of Wnt/β-catenin pathway in TNBC patients. In breaking the Achilles’ heel of this positive feedback loop and thereby weaken Wnt/β-catenin activity, we hope to achieve a much favorable outcome in TNBC patients.