159P - Dead/H (ASP-GLU-ALA-ASP/HIS) Box Polypeptide 3, X-Linked Plays an Oncogenic Roles to Induce Cancer Stem Cell-Like Properties

Abstract

ABSTRACT Background DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is a member of the DEAD-box family of ATP dependent RNA helicase. DEAD-box helicases have multiple functions including RNA splicing, mRNA export, transcriptional and translational regulation, RNA decay, and ribosome biogenesis. In the last ESMO meeting, we demonstrated that DDX3X is one of 4 proteins that are specifically expressed in CD133+ B16 melanoma cells, which possess cancer stem cell (CSC) properties and that a DDX3X vaccination induced antitumor therapeutic immunity against parental melanoma. DDX3X is evolutionarily well conserved from yeast to humans, suggesting that it is essential for cell survival. In humans, DDX3X deletion or dysfunction results in genetically related primary amenorrhea and impaired female fertility. Although DDX3X was originally reported to suppress growth by modulating p21waf/cip1 gene expression, it has been recently shown that DDX3X is directly correlated with oncogenesis. Furthermore, it has been shown that DDX3X over-expression in breast cancer cells facilitates β-catenin signal transduction and induces epithelial mesenchymal transition (EMT), a known feature of CSC. However, a precise mechanism how DDX3X, a RNA helicase, plays an oncogenic role to induce CSC features is still uncertain. Results Immunoblotting analyses revealed that all of the examined cancer cells, including lung cancer, colon cancer and breast cancer cells expressed DDX3X, while normal human epidermal keratinocytes (NHEK), human microvascular endothelial cells (HMEC), and normal human bronchial epithelial cells (NHBE) faintly expressed DDX3X. Moreover, putative CSC marker positive cancer cells, such as 87.5, HCT116, and MCF7, strongly expressed DDX3X. HCT116 cells, which have CD133 and strong DDX3X expression, exhibit CSC like properties, such as high tumorgenicity, growth as non-adherent spheres, and aggressive invasion ability. Knockdown of DDX3X resulted in loss of CSC-like features. We found that epigenetic regulation by DDX3X play a critical role in oncogenesis. Conclusion DDX3X plays an important role in inducing CSC properties. Disclosure H. Kagamu: I received research fund from Otsuka Phamaceutical Co., Ltd. All other authors have declared no conflicts of interest.