Browsing by Subject "Cytoskeletal proteins"

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    Profiling the interactome of STK10 by using proximity-based biotinylation
    (2023-05) Carus, Yağmur Öykü
    Breast cancer accounts for a quarter of all newly diagnosed cancer cases globally in women. It is also the primary cause of death in female cancer patients. In 2020, it was responsible for 15% of all cancer-related deaths in women. The PI3K pathway is the most commonly deregulated pathway in breast cancer. As a result, numerous inhibitors for druggable targets within the pathway have been developed. Unfortunately, drug resistance is frequently observed after treatment with these inhibitors. The mechanisms behind this resistance are widely studied. AKT has been known to be the kinase responsible for transmitting the signal to downstream targets. However, new studies suggested there can be AKT-independent kinases relaying the signal to downstream targets causing PI3K inhibitor drug resistance. Previously, our group hypothesized that they could find an AKT-independent protein that confers resistance to PI3K inhibition. Their bioinformatical analyses identified STK10 (Serine-Threonine Kinase 10) as a possible druggable target for PI3K pathway inhibitor resistance in an AKT-independent manner. They performed wet lab experiments to show STK10’s impact on PI3K inhibitor resistance in breast cancer. They showed STK10 knock-down sensitizing resistant breast cancer cells to PI3K inhibitor. Although their experiments supported the hypothesis of STK10 affecting the PI3K inhibitor resistance of breast cancer cells, they could not identify the molecular mechanisms behind this interaction. In this study, by using APEX2 proximity-based biotinylation followed by mass spectrometry, we profiled STK10’s interactome. We aimed to understand how STK10 contributes to the progression of breast cancer and the development of resistance to treatment. Our bioinformatics analyses indicated possible interaction between STK10 and the candidate proteins we obtained from our mass spectrometry analysis. Immunofluorescence and Co-IP experiments supported some of the putative interactions we discovered. The proteins discovered near STK10 were primarily linked to the reorganization of the cytoskeleton, which is encouraging since STK10 is recognized for its involvement in cell migration through the phosphorylation of ERM proteins. Based on our observations, it is possible to hypothesize that STK10 is influencing the cytoskeletal reorganization in breast cancer cells. However, further experiments are needed to be done to understand the molecular mechanisms behind STK10’s possible functions in breast cancer. These experiments could lead to uncovering the role of STK10 in PI3K inhibitor resistance and help us to identify new therapeutic options to battle breast cancer.