Abstract 1139: An shRNA screening reveals that the tumorigenic effect of FBXO11 is inversely correlated with EMT profiles in breast cancer

Abstract

Abstract Over the last decade a trend to study cancer stem cells (CSCs) has become synonymous to studying epithelial to mesenchymal transition (EMT), and has emerged in the field of breast cancer research. In turn, tumorigenesis of epithelial luminal-like breast cancer has been largely overlooked. Recently however, we and others have provided evidence that tumorigenic capacity is not always restricted to EMT-like cancer cells. Furthermore, the metastatic feature is conveyed by subclones of phenotypically differentiated non-EMT cancer cells. In this study, we aimed to identify the differential tumorigenic mechanisms of more aggressive non-EMT cells against the less aggressive EMT cells in breast cancer. By using loss of function screening, we found that a member of the E3 ubiquitin ligase complexes, FBXO11, facilitates tumor formation of non-EMT like cells by inhibiting the p53/p21 pathway. More importantly, our data showed that roles of FBXO11 in tumorigenesis are highly cell-type dependent. In conclusion, our study empathizes that it is important to understand the complexities of individual tumors in the development of personalized therapy. Citation Format: Jiyoung Kim, Sofie O. Bagger, Branden B. Hopkinson, René Villadsen, Ole W. Petersen. An shRNA screening reveals that the tumorigenic effect of FBXO11 is inversely correlated with EMT profiles in breast cancer [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 1139.