Phosphoglycerate dehydrogenase induces glioma cells proliferation and invasion by stabilizing forkhead box M1.
Phosphoglycerate dehydrogenase induces glioma cells proliferation and invasion by stabilizing forkhead box M1.
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磷酸甘油酸脱氢酶通过稳定叉头盒M1诱导胶质瘤细胞增殖和侵袭
DOI：
10.1007/s11060-012-1018-x
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发表时间：
2013-02
影响因子：
3.9
通讯作者：
Zhang, Nu
中科院分区：
文献类型：
--
作者：
Liu, Jinlong;Guo, Shaolei;Li, Qingzhi;Yang, Lixuan;Xia, Zhibai;Zhang, Longjuan;Huang, Zhengsong;Zhang, Nu
磷酸甘油酸脱氢酶（PHGDH）是三步丝氨酸生物合成途径中糖酵解分支的第一个酶。最近的证据表明，PHGDH在人类乳腺癌和黑色素瘤中被放大，并在癌症代谢中发挥关键作用。然而，PHGDH在胶质瘤中的表达及其在肿瘤发生中的潜在非代谢作用尚未报道。我们分析了神经胶质瘤患者标本中的PHGDH水平，发现PHGDH虽然在正常脑组织中呈阴性，但在星形细胞肿瘤中高表达，并且在更具侵袭性的癌症类型中表达越来越多。抑制胶质瘤细胞中PHGDH的表达可下调VEGF、MMP-2、CHK2和cyclin D1的表达，降低胶质瘤细胞体外和体内的增殖、侵袭和致瘤性。有趣的是，我们发现在phdgh沉默的胶质瘤细胞中，致癌转录因子FOXM1也下调。通过LC/LC MS分析，我们确定了PHGDH是FOXM1的一个新的结合伙伴。PHGDH在蛋白水平上与FOXM1相互作用并稳定FOXM1，促进胶质瘤细胞的增殖、侵袭和致瘤性。我们的数据确定了PHGDH是神经胶质瘤的潜在预后标志物，并确定了PHGDH在神经胶质瘤发生中的非代谢作用，为未来脑肿瘤治疗提供了靶向PHGDH - foxm1轴的新角度。
Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme branching from glycolysis in the three-step serine biosynthetic pathway. Recent evidence has shown that PHGDH is amplified in human breast cancer and melanoma and plays a key role in cancer metabolism. However, PHGDH expression in glioma and a potential non-metabolic role in tumorigenesis have not been reported. We analyzed PHGDH levels in specimens from glioma patients and found that PHGDH, although negative in normal brain tissues, was highly expressed in astrocytic tumors and increasingly expressed in more aggressive cancer types. Inhibition of PHGDH expression in glioma cells downregulated the expression of VEGF, MMP-2, CHK2 and cyclin D1 and reduced glioma cell proliferation, invasion and tumorigenicity in vitro and in vivo. Interestingly, we found that the oncogenic transcription factor FOXM1 was also downregulated in PHDGH-silenced glioma cells. Using LC/LC MS analysis, we identified PHGDH as a novel binding partner of FOXM1. PHGDH interacted with and stabilized FOXM1 at the protein level, promoting the proliferation, invasion and tumorigenicity of glioma cells. Our data identified PHGDH as a potential prognostic marker of glial brain tumors and identified a non-metabolic role for PHGDH in glioma tumorigenesis, providing a novel angle of targeting the PHGDH–FOXM1 axis in future brain tumor therapy.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
4.5
作者：
Nilsson LM;Forshell TZ;Rimpi S;Kreutzer C;Pretsch W;Bornkamm GW;Nilsson JA
通讯作者：
Nilsson JA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
50.3
作者：
Zhang N;Wei P;Gong A;Chiu WT;Lee HT;Colman H;Huang H;Xue J;Liu M;Wang Y;Sawaya R;Xie K;Yung WK;Medema RH;He X;Huang S
通讯作者：
Huang S
影响因子：
11.2
作者：
Zhang, Yujian;Zhang, Nu;Dai, Bingbing;Liu, Mingguang;Sawaya, Raymond;Xie, Keping;Huang, Suyun
通讯作者：
Huang, Suyun