TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000434821
  • Gene Name:ACVR1
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:BMP signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00313 (APRD00256, DB00510, APRD00066)
  • Drug Name:Valproic acid
  • Drug Method:inhibit the histone deacetylation to up-regulated the gene expression

Disease basic infommation

  • Disease:glioma
  • Tissue:cell lines (TGS-01 and TGS-04)

Other information

  • Title:Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells
  • Journal:Oncogene
  • Published:2017
  • PubMed ID:28459464
  • Abstract:Bone morphogenetic protein (BMP) signaling exerts antitumor activities in glioblastoma; however, its precise mechanisms remain to be elucidated. Here, we demonstrated that the BMP type I receptor ALK-2 (encoded by the ACVR1 gene) has crucial roles in apoptosis induction of patient-derived glioma-initiating cells (GICs), TGS-01 and TGS-04. We also characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of GICs. The tumor-suppressive effects of ALK-2 and DLX2 were further confirmed in a mouse orthotopic transplantation model. Interestingly, valproic acid (VPA), an anti-epileptic compound, induced BMP2, BMP4, ACVR1 and DLX2 mRNA expression with a concomitant increase in phosphorylation of Smad1/5. Consistently, we showed that treatment with VPA induced apoptosis of GICs, whereas silencing of ALK-2 or DLX2 expression partially suppressed it. Our study thus reveals BMP-mediated inhibitory mechanisms for glioblastoma, which explains, at least in part, the therapeutic effects of VPA.
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