Project description:Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss of chromosome 10 and aberrantly activated RTK signaling pathways. Here, we identify mesenchymal homeobox 2 (MEOX2) as a salient oncogenic transcription factor candidate with increased expression in GBMs. Our results suggest that MEOX2 can enhance ERK signaling through a feed-forward mechanism. We show that MEOX2 overexpression can lead to increased growth in bona fide GBM implantation models and cooperates with loss of p53 and PTEN in cerebral organoid models of human malignant gliomas to induce cell proliferation. Furthermore, using high-throughput genomics, we identify transcriptional target genes of MEOX2 in patient-derived GBM tumorsphere models and a fresh frozen GBM tumor.
Project description:Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss of chromosome 10 and aberrantly activated RTK signaling pathways. Here, we identify mesenchymal homeobox 2 (MEOX2) as a salient oncogenic transcription factor candidate with increased expression in GBMs. Our results suggest that MEOX2 can enhance ERK signaling through a feed-forward mechanism. We show that MEOX2 overexpression can lead to increased growth in bona fide GBM implantation models and cooperates with loss of p53 and PTEN in cerebral organoid models of human malignant gliomas to induce cell proliferation. Furthermore, using high-throughput genomics, we identify transcriptional target genes of MEOX2 in patient-derived GBM tumorsphere models and a fresh frozen GBM tumor.
