Abstract CN08-02: BMP signaling in glioblastoma

Glioma-initiating cells (GICs) play central roles in the initiation, progression, recurrence, tumor heterogeneity and drug resistance of glioblastoma. Bone morphogenetic proteins (BMPs) regulate normal embryonic neural development and exert anti-tumor activities in glioblastoma. However, its mechanisms of action remain to be elucidated. Through RNA-seq analyses, we have identified several BMP-target genes in GICs, including SMAD6, Noggin (NOG), Distal-less homeobox 2 (DLX2), and Paired-related homeobox 1 (PRRX1). DLX2 promotes apoptosis and neural differentiation of GICs. We also show that the expression of PRRX1 is induced by BMP stimulation, and that PRRX1 induces decrease in the CD133-positive GIC population and inhibits in vivotumorigenic activity of GICs. Of the two spliced isoforms of PRRX1, the longer form of PRRX1, but not the shorter form, is involved in the induction of differentiation of GICs through epigenetic regulation of the CD133/PROM1gene. In addition, we show that BMP-4 represses the expression of a transmembrane protein, which is preferentially expressed in mesenchymal subtype of glioblastoma. Potential use of these proteins for diagnosis and treatment of glioblastoma will be discussed. Citation Format: Kohei Miyazono, Ryo Tanabe. BMP signaling in glioblastoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr CN08-02. doi:10.1158/1535-7163.TARG-19-CN08-02