Evaluation of a cell migration- and autophagy-related kinase as a novel drug target in pediatric glioma

Pediatric gliomas are aggressive brain tumors that pose serious difficulties in terms of prognosis and treatment options. The purpose of this thesis is to assess a novel therapeutic target for pediatric glioma, a cell migration- and autophagy-related kinase. This kinase was discovered as a prospective therapeutic target by a thorough study of proteomic datasets due to its altered expression and interaction with important pathways involved in cell migration and autophagy in glioblastoma. This thesis examines the functional importance and expression of the discovered kinase in pediatric glioma cell lines and patient tumour samples. We observed that migration and drug resistance of pediatric glioma cells are more sensitive to changes in autophagic flux. Also, its expression and localization in patient samples is evaluated using quantitative PCR, Western blotting, and immunohistochemistry. To determine the influence of targeting this kinase on glioma cell migration and autophagy, functional tests such as cell migration assays, autophagy flux analysis, and cell viability assays were carried out. The findings from this study could aid in facilitating the improvement of pediatric glioma-targeted treatments. Understanding the functions of this kinase protein will help researchers develop novel pharmaceutical candidates that selectively limit the growth of gliomas while minimizing side effects. The interaction between the interested kinase protein and one of the main autophagy proteins, ATG5, was displayed. The changes in the autophagic degradation with wild-type, kinase overexpressing and CRISPR-Cas9 mediated knockout cell lines were revealed. Moreover, cellular migration was significantly influenced upon depletion of the protein. Besides, drug resistance against various commonly used chemotherapeutic agents was not changed with gene deletion and kinase inhibition. To summarize, this research on the interested kinase protein as a druggable target may pave the door for individualized treatment plans that develop the prognosis and quality of life for children with gliomas.