Memeli hücrelerde protokadherinlerin rollerinin araştırılması

Cancer is one of the leading causes of morbidity and mortality around the globe. It is a complex disease characterized by hyperproliferation, genetic instability causing cumulative mutations, and at advanced stages spread to secondary sites, through a process known as metastasis. Metastasis is directly dependent on cancer cells' ability to migrate and, for an intervention in metastasis, it is pertinent to understand the molecular details of cell migration. In the current thesis, we attempted to understand the roles of a cell surface protein protocadherin-7 (PCDH7) in cell migration. Previous work from our group has shown PCDH7 as a cell-cycle regulated membrane protein. In current thesis, we characterized the effects of perturbation of PCDH7 expression on cell migration of mammalian cells in culture, and its role in the cortical migration of neuronal progenitors during embryonic development using in-utero electrophoresis. We also characterized its sub-cellular localization using fixed sample imaging and live-cell imaging, which highlighted its association with cellular compartments directly involved in cell migration dynamics. To further characterize molecular mechanisms behind PCDH7's role in cell migration, we used a quantitative proteomics approach to compare global changes upon PCDH7's knockout which outlines a plethora of upregulated and downregulated proteins. Many of these proteins have previously been shown to be associated with cellular compartments involved in cell migration or have a molecular function characterized in the regulation of cell migration. Taken together, our work outlines a critical role of PCDH7 in cell migration, association with migration-associated subcellular compartments, and possible molecular players in its role. Our work is a step towards recognizing PCDH7 as a promising therapeutic target for control of cancer metastasis.