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[P1-06-07] Msi1 in maintaining breast cancer stem cell involves the AKT/PI3K pathway. Nahas GR, Sinha GA, Sherman LS, Walker ND, Rameshwar P. Rutgers University-Graduate School of Biomedical Sciences, Newark, NJ. Musashi1 (Msi1) was originally described in neural stem cells in a role influencing neural differentiation in the Numb/Notch pathway. Due to its role in neural stem cells, there has been much interest in the role of Msi1 in the breast cancer (BC) stem cell population. In this vein, with we have demonstrated a possible feedback loop between the stem cell marker OCT4 and Msi1, in addition to other stem cell-associated genes. Flow cytometry analyses demonstrated that the subset of BC cells (BCCs) that we previously identified as those with high Oct4 was also enriched for Msi1. Msi1 knockdown BCCs showed decreased doubling time and with limited ability to be passaged, indicating the loss of the self-renewal subset needed for cell passaging. These in vitro findings were consistent with the inability of the Msi1 knockdown BCCs to undergo serial passages in vivo. We therefore examined the Msi1 knockdown BCCs for intracellular proteins that could explain the reduced cell growth and the reduced initiating cells. We selected the AKT/PI3K pathway due to its recent connection to the maintenance of BC stem cells. Msi1 knockdown repressed several molecules within the AKT/PI3K pathway: PTEN, AKT, and PI3K. There were no significant differences found however, in the apoptotic factors, BCL-2 and Caspase-3. Upon further investigation, we observed increases in molecules that are linked to decreased cell proliferation and senescence, p16, p53 and p21. Since Msi1 is an RNA binding protein, it is possible that its loss could leave RNAs for binding to miRNAs and this might be partly responsible for the decrease in key intracellular molecules needed for the survival and proliferation of the Msi1 knockdown BCCs. Further studies are needed to investigate how miRNAs and Msi1 interact to maintain the survival of BCCs. Finally, Msi1 KD positively affects the expression of the immune checkpoint inhibitor PD-1L, suggesting increased PD-1L expression in cells that are not of the CSC phenotype. The studies may identify Msi1 or its associated molecules as a potential therapeutic intervention for BC. Wednesday, December 9, 2015 5:00 PM Poster Session 1: Tumor Cell and Molecular Biology: Stem/Progenitor Cells (5:00 PM-7:00 PM) ↓ 海报下载（文件大小：841KB） |
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