Yasui, Linda S.
B.A. (Bachelor of Arts)
Department of Biological Sciences
Glioblastoma multiforme (GBM) is a deadly form of brain cancer, with an expected survival of only a few months after diagnosis without therapy. The current standard of care extends life expectancy by a couple of months due to almost universal recurrence of the tumor. Recurrence of GBM is highly dependent on a radiation-resistant subpopulation of GBM, the cancer stem cells (CSCs). CSCs possess an enhanced ability to repair therapy-induced DNA damage, especially DNA double strand breaks (DSBs). To study the role of DNA damage repair in GBM CSCs, our investigations used a knockout (KO) of an enzyme, DNA PKcs, which plays a key role in the repair of DNA double strand breaks. Surprisingly, we discovered that autophagy (assayed by the direct visualization of autophagosomes) wasprofoundly affected by DNA PKcs KO in GBM cells and GBM CSCs. Furthermore, exposure of these cells to 2Gy irradiation caused another shift in autophagy. Changes in mitochondrial morphology raised questions regarding energy metabolism, prompting the use of an ATP assay that indicated increased energy requirements in cells lacking DNA-PKcs. These results point to a role for cancer cell energy metabolism and cancer stem cell metabolism in the cells’ therapeutic response, emphasizing the importance of understanding the stress responses of GBM cells and GBM cancer stem cells to improve radiation treatment against cancer.
Diulus, Samantha C., "Autophagy in DNA-PKcs Knockout Glioblastoma Cancer Stem Cells" (2019). Honors Capstones. 215.
Northern Illinois University
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