COLUMBUS, Ohio – A study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) sheds light on how tumor cells maintain the balance of cholesterol in their membranes and provides a promising avenue for developing new treatments for glioblastoma, the most lethal brain cancer.    Study findings are published online in the journal Cell Reports.    Cholesterol is a waxy substance and acts as an essential structural component of cell membrane. In certain types of cancer, including glioblastoma, excess cholesterol is stored in lipid droplets within the cells. Since tumors grow rapidly and need proper levels of cholesterol in their cell membranes to survive, targeting cholesterol regulation could be a potential strategy for anti-tumor therapy.    Autophagy is a natural process that helps cells recycle nutrients under starvation or stressful conditions. In this study, the researchers made a significant discovery: a key gene called SREBP-1, which is long-termly thought only regulating de novo lipid synthesis, becomes active when cellular cholesterol levels drop, actually promotes autophagy. This process helps break down the stored cholesterol in lipid droplets, releasing it to maintain the necessary cholesterol levels in cell membranes.   “By targeting the SREBP-1 gene and the autophagy process, it might be possible to significantly disrupt the cholesterol supply to cancer cells and suppress their growth. This research opens exciting possibilities for future glioblastoma therapies,” said lead author Deliang Guo, PhD, a member of the OSUCCC – James Translational Therapeutics Research Program and professor at Ohio State’s College of Medicine, and founding Director of the newly established Center for Cancer Metabolism in OSUCCC, where he holds the Urban and Shelley Meyer Professorship in Cancer.     Researchers examined clinical human glioblastoma specimens and cells in this study. Glioblastoma is highly aggressive and the most common primary malignant brain tumor in adults. Despite the advanced diagnosis and ideal treatment including surgery, followed by radiotherapy plus temozolomide chemotherapy, the median survival is only around 15 months.     “Further detailed understanding of glioblastoma tumor progress and emerging therapeutic strategies are urgently needed. Our findings unravel a novel understanding of how glioblastoma cells maintain the membrane cholesterol levels and provide a promising potential therapeutic avenue by disrupting hydrolysis of stored cholesterol through suppression of SREBP-1 mediated lipid droplet autophagy,” said Feng Geng, PhD, first author and a research scientist with the Department of Radiation Oncology and Center for Cancer Metabolism and the College of Medicine.    OSUCCC – James coauthors include Yaogang Zhong, PhD, Huali Su, PhD, and Arnab Chakravarti, MD. Other coauthors include Etienne Lefai with the University Clermont Auvergne in France, Shino Magaki, MD, PhD, and Timothy F. Cloughesy, MD, with the University of California, Los Angeles and William H. Yong with University of California, Irvine, California.    This work was supported by the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, and the American Cancer Society, along with a Pelotonia Idea grant and the Urban and Shelly Meyer Foundation.     # # #   Media Contact: Eileen Scahill, Media Relations, Eileen.Scahill@osumc.edu