Abstract 4454: Ecdysoneless, a novel regulator of cell cycle progression and oncogenesis

Precisely regulated cell proliferation is essential for embryonic development and for homeostasis in adult organs and tissues, whereas uncontrolled cell proliferation is a hallmark of cancer. We have identified the human orthologue of Drosophila Ecdysoneless (ECD) as a critical regulator of cell cycle progression and oncogenesis. ECD is overexpressed in cancers of several organs, and its overexpression correlates with shorter survival in breast cancer patients. Overexpression of ECD leads to an oncogenic phenotype in immortal mammary epithelial cells. ECD deletion in breast cancer cells on the other hand decreased the in vitro oncogenic phenotype and the in vivo tumorigenesis. Mechanistically, we showed that ECD associates with a protein complex called R2TP, composed of RUVBL1, RUVBL2, RPAP3, PIHID1 proteins, which is involved in several biological functions, including the dynamic assembly of protein-protein and protein-RNA complexes. In addition, affinity purification followed by Mass Spec analyses showed that ECD binds to several proteins, including PRPF8, that are components of critical protein complexes required for RNA splicing. Based on these findings, we hypothesize that ECD interacts with the R2TP complex and protein complexes that control key steps in the cellular mRNA processing. We hypothesize that these complexes are required for the overexpressed ECD to regulate mRNA processing to promote cell proliferation and cell survival in cancer cells. We will present data to document the ECD complexes required for cell cycle regulation and cell survival. Our studies reveal novel roles of ECD in cancer cells, and support the rationale for use of overexpression of ECD and its interacting proteins as molecular biomarkers of tumor progression as well as explore the targeting of these complexes to develop novel cancer therapy agents. Citation Format: Irfana Saleem, Sameer Mirza, Aniruddha Sarkar, Hamid Band, Vimla Band. Ecdysoneless, a novel regulator of cell cycle progression and oncogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4454.