Functional study of mammary epithelial cell architecture
Cell organization confers cellular identity and guides cellular functions. Here, the cell organization is defined as the global arrangement of the functional complexes, which are composed of proteins, nucleic acids, lipids, or the combinations of any of them, in the cells. These functional complexes are arranged in a spatial and temporal manner, which closely reflects and regulates cellular activities. Targeting two proteins that act as central nodes in the nucleus, the nuclear mitotic apparatus protein, NuMA, and in the cytoplasm, the CDP-diacylglycerol synthase 1, CDS1, I have studied their influences on two features of the cell architecture, namely the nucleolus and the polarity axis, that play a major role in the homeostasis of mammary epithelial cells and in cancerous development. The nucleolus is an essential nuclear bodywith functions in ribosome biosynthesis, stress perception, and cell cycle control. Basoapical polarity is the signature structure of the differentiated epithelial cells and is functionally related to cell proliferation and survival. By modulating the expression of NuMA or of CDS1 and assessing the resulting impact on the nucleolus or the tissue polarity axis, respectively, my goal was to further the understanding of the regulation and role of these architectural features in cell phenotypes. I have shown in my major project that NuMA is involved in the control of nucleolar architecture and rDNA transcription. I also showed in my minor project that CDS1 partially restores basal polarity depending on signaling in aggressive MDA-MB- 213 cancer cells. I have placed these studies focused on cellular architecture in the context of cancer prevention, from its onset to progression.
Lelievre, Purdue University.
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