Abstract LB-183: Investigating the role of polarity protein, SCRIB, in hematopoiesis

Acting as both a polarity regulator and a scaffolding protein, Scribble (SCRIB), coordinates intracellular signalling pathways that regulate cell proliferation, migration and apoptosis. Deregulation of SCRIB has been linked to multiple epithelial cancers but the role of SCRIB in hematopoiesis and hematopoietic malignancies remains relatively unexplored. Using different approaches, we show that SCRIB is expressed in hematopoietic stem and progenitor cells and in their differentiated progenies, implying a role for SCRIB in blood production. We investigated the effect of SCRIB loss in hematopoiesis using two conditional knockout mouse models in conjunction with an extensive phenotypic labelling regime and multi-color flow cytometry. We reveal a role for SCRIB in T cell development although subtle differences between the two mouse models were noted. Compensatory mechanisms often mask the effects of single protein deletion during steady-state so stress hematopoiesis was induced through a transplant assay to minimise these effects. Lethally irradiated recipient mice receiving a transplant of SCRIB knockout bone marrow revealed a more striking phenotype with significantly altered populations of granulocyte, macrophage, erythroid, T and B cell progenitors, and mature macrophage fractions compared to controls. Collectively, our data shows SCRIB is required for the development of multiple hematopoietic fractions and studies are currently underway to identify the underlying mechanism/s and elucidate how deregulation of SCRIB impacts on hematopoietic malignancies. Citation Format: Novita Novita, Alysha Dew, Chad Johnson, Carl R. Walkley, Louise E. Purton, Patrick O. Humbert, Phillip K. Darcy, Sarah L. Ellis. Investigating the role of polarity protein, SCRIB, in hematopoiesis [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 LB-183.