Abstract 5494: Targeting deregulated expression and function of Mitofusin 1 in glioblastoma

Glioblastoma (GBM) is the most common form of adult primary malignant brain tumor with a poor prognosis. Despite advances in standard treatments, such as surgery, radiation, and adjuvant chemotherapy, outcome remains poor. To further develop effective therapeutic approaches, it is essential to garner a better understanding of GBM progression. Substantial research has shown that GBM's progression is associated with metabolic remodeling, that includes the use of aerobic glycolysis as the main source of energy. Here, we report the novel role of Mitofusin 1 (MFN1), a key regulator of mitochondrial outer membrane fusion in glycolysis. We first established that MFN1 is highly expressed in GBM when compared to its isoform MFN2 using TCGA (The Cancer Genome Atlas) and OncomineTM glioma datasets. Silencing MFN1 using MFN1-shRNA in GBM10 cells showed decreased expression levels of PDK1 and HIF1-alpha as observed in western blotting and RT-PCR analysis. Interestingly, c-myc expression was significantly reduced in the shMFN1 treated GBM 10 cell. In addition, RNASeq analysis conducted on shPDK1 treated GBM-10 cells revealed reduced MFN1 levels. Further silencing of MFN1 showed increased OCR and decreased ECAR using seahorse XFp bio analyzer. Collectively, our preliminary data points to MFN1 as a candidate metabolic oncogene in GBM, and targeting MFN1 will be a novel GBM treatment. Citation Format: Maheedhara Reddy Guda, Swapna Asuthkar, Collin M. Labak, Chase P. Smith, Andrew J. Tsung, Kiran Velpula. Targeting deregulated expression and function of Mitofusin 1 in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5494.