Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
EMBO Rep. 2018 Nov;19(11). doi: 10.15252/embr.201745587. Epub 2018 Sep 13.
Glioblastoma is one of the most aggressive forms of cancers and has a poor prognosis. Genomewide analyses have revealed that a set of core signaling pathways, the p53, RB, and RTK pathways, are commonly deregulated in glioblastomas. However, the molecular mechanisms underlying the tumorigenicity of glioblastoma are not fully understood. Here, we show that the lysine deacetylase SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells, including glioblastoma stem cells. Furthermore, we demonstrate that SIRT2 regulates p73 transcriptional activity by deacetylation of its C-terminal lysine residues. Our results suggest that SIRT2-mediated inactivation of p73 is critical for the proliferation and tumorigenicity of glioblastoma cells and that SIRT2 may be a promising molecular target for the therapy of glioblastoma.
胶质母细胞瘤是最具侵袭性的癌症之一，预后不良。全基因组分析表明，一组核心信号通路，包括 p53、RB 和 RTK 通路，在胶质母细胞瘤中通常失调。然而，胶质母细胞瘤的致瘤机制尚不完全清楚。在这里，我们表明赖氨酸去乙酰化酶 SIRT2 是胶质母细胞瘤细胞（包括胶质母细胞瘤干细胞）增殖和致瘤所必需的。此外，我们证明 SIRT2 通过去乙酰化其 C 末端赖氨酸残基来调节 p73 的转录活性。我们的结果表明，SIRT2 介导的 p73 失活对于胶质母细胞瘤细胞的增殖和致瘤性至关重要，并且 SIRT2 可能是胶质母细胞瘤治疗的有前途的分子靶点。
