例如:"lncRNA", "apoptosis", "WRKY"

Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells.

Oncogene. 2017 Aug 31;36(35):4963-4974. Epub 2017 May 01
E Raja 1 , A Komuro 1 , R Tanabe 1 , S Sakai 1 , Y Ino 2 , N Saito 3 , T Todo 2 , M Morikawa 1 , H Aburatani 4 , D Koinuma 1 , C Iwata 1 , K Miyazono 1
E Raja 1 , A Komuro 1 , R Tanabe 1 , S Sakai 1 , Y Ino 2 , N Saito 3 , T Todo 2 , M Morikawa 1 , H Aburatani 4 , D Koinuma 1 , C Iwata 1 , K Miyazono 1
+ et al

[No authors listed]

Author information
  • 1 Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 2 Division of Innovative Cancer Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • 3 Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 4 Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.

摘要


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.