Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma.
Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma.
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DOI：
10.18632/oncotarget.3262
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发表时间：
2015-03-30
期刊：
影响因子：
--
通讯作者：
Yun JP
中科院分区：
文献类型：
--
作者：
Hu W;Lu SX;Li M;Zhang C;Liu LL;Fu J;Jin JT;Luo RZ;Zhang CZ;Yun JP
丙酮酸激酶M2(PKM2)参与了华宝效应，这是癌症的一个标志。我们发现PKM2水平与总生存率(危险比=1.675，95%可信区间：1.389-2.019，P<；0.001)和无病生存率(危险比=1.573，95%可信区间：1.214-2.038，P<；0.001)相关。这种相关性在148名肝细胞癌患者的独立队列中得到进一步验证。多变量分析显示，PKM2是肝细胞癌预后不良的独立指标。在体内外，肝癌细胞中PKM2基因的敲除抑制了细胞的增殖并诱导了细胞的凋亡。BIM siRNA可明显阻断PKM2耗竭诱导的细胞凋亡。PKM2的耗竭降低了Bim的降解。在临床标本中，PKM2的表达与Bim的表达呈负相关。联合检测PKM2和Bim的预后意义最好。我们认为PKM2可作为肝癌患者预后不良的生物标志物，其基因敲除可通过稳定Bim而诱导肝癌细胞凋亡。
Pyruvate kinase M2 (PKM2) contributes to the Warburg effect, a hallmark of cancer. We showed that PKM2 levels were correlated with overall survival (hazard ration = 1.675, 95% confidence interval: 1.389–2.019, P < 0.001) and disease-free survival (hazard ration = 1.573, 95% confidence interval: 1.214–2.038, P < 0.001) in a cohort of 490 patients with HCC. The correlations were further validated in an independent cohort of 148 HCC patients. Multivariate analyses revealed that PKM2 was an independent indicator of poor outcome in HCC. The knockdown of PKM2 in HCC cells inhibited cell proliferation and induced apoptosis in vitro and in vivo. Bim siRNA markedly abolished the PKM2-depletion-induced apoptosis. PKM2 depletion decreased the degradation of Bim. In clinical samples, PKM2 expression was reversely correlated with Bim expression. Combination of PKM2 and Bim levels had the best prognostic significance. We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.
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DOI：
10.1016/j.biocel.2007.11.009
发表时间：
2008-01-01
影响因子：
4
作者：
Lee, Jungwoon;Kim, Hye Kyoung;Kim, Jungho
通讯作者：
Kim, Jungho
影响因子：
3.5
作者：
Salvioli, S;Ardizzoni, A;Cossarizza, A
通讯作者：
Cossarizza, A
BimL 直接中和 Bcl-xL，促进 UV 诱导细胞凋亡过程中的 Bax 激活
影响因子：
3.5
作者：
Wang, Xianwang;Xing, Da;Chen, Wei R.
通讯作者：
Chen, Wei R.
DOI：
10.1016/j.bbrc.2012.05.063
发表时间：
2012-06-22
影响因子：
3.1
作者：
Kwon, Oh-Hyung;Kang, Tae-Wook;Kim, Yong Sung
通讯作者：
Kim, Yong Sung
DOI：
10.1084/jem.20111487
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goldberg MS;Sharp PA
通讯作者：
Sharp PA