Memeli sitokinezi ve hücresel farklılaşmanın altında yatan moleküler mekanizmalar

Cytokinesis is the last step of eukaryotic cell division, where actin cytoskeleton, plasma membrane and cell division machinery interact to physically separate newly forming daughter cells. Any mistake during this process may transform normal cells into cancer cells. However, as a highly complex mechanism, mammalian cytokinesis has still many fundamental questions that need to be answered. Our previous proteomic analysis suggested a role of chloride intracellular channel (CLIC) proteins during cytokinesis. In the first part of this study, a mass spectrometry based systematic analysis of proximity interactome revealed novel cytokinesis related interaction partners of CLIC4. We found that these interactions enhance the fidelity of cytokinesis. In the second part, a quantitative proteomic approach was used to systematically analyze the biochemical changes that drive differentiation of human mammary epithelial cells into mesenchymal cells. Normally, the epithelial-mesenchymal transition (EMT) plays a central role in embryonic development; however, cells may use EMT as a way of cellular differentiation to facilitate the initiation and progression of metastasis and carcinogenesis. So far, several studies have been confined to the transcriptional regulation of EMT. However, transcriptome analysis may not thoroughly predict the regulation at the protein level due to post-transcriptional modifications. As a result of our proteomic analysis, several novel mRNA and/or protein level modulators of EMT were identified and validated by in vitro and in vivo experiments. Among these, we revealed DNAJB4 and CD81 as novel metastasis inducers in breast cancer. This work also provides a unique platform and resource for future studies focusing on metastasis and carcinogenesis.