PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer.
PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer.
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DOI：
10.1038/sj.bjc.6604356
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发表时间：
2008-06-17
影响因子：
8.8
通讯作者：
Harris, A. L.
中科院分区：
文献类型：
--
作者：
Wigfield, S. M.;Winter, S. C.;Giatromanolaki, A.;Taylor, J.;Koukourakis, M. L.;Harris, A. L.
关键词：
在这里，我们描述了HIF-1调节的蛋白丙酮酸脱氢酶激酶-1(PDK-1)在头颈部鳞癌(HNSCC)中的表达和功能。用RNA干扰技术下调低氧诱导的PDK1，我们发现低氧16-48 h后乳酸和丙酮酸的排泄被抑制到常氧水平。这表明PDK-1在维持糖酵解中起着重要作用。在低氧条件下，基因敲除对细胞增殖和存活无影响。采用免疫组织化学方法检测140例HNSCC组织中PDK-1的表达。PDK-1在正常组织中不表达，但在HNSCC中表达上调，主要为胞浆表达，偶见局灶性核表达。这与不良预后密切相关(P=0.005，中位数分裂)。这些结果表明，低氧诱导因子对PDK-1的调节在维持人类癌症中乳酸的产生中起着关键作用，因此应该研究PDK-1抑制剂的抗肿瘤作用。
Here we describe the expression and function of a HIF-1-regulated protein pyruvate dehydrogenase kinase-1 (PDK-1) in head and neck squamous cancer (HNSCC). Using RNAi to downregulate hypoxia-inducible PDK-1, we found that lactate and pyruvate excretion after 16–48 h of hypoxia was suppressed to normoxic levels. This indicates that PDK-1 plays an important role in maintaining glycolysis. Knockdown had no effect on proliferation or survival under hypoxia. The immunohistochemical expression of PDK-1 was assessed in 140 cases of HNSCC. PDK-1 expression was not expressed in normal tissues but was upregulated in HNSCC and found to be predominantly cytoplasmic with occasional strong focal nuclear expression. It was strongly related to poor outcome (P=0.005 split by median). These results indicate that HIF regulation of PDK-1 has a key role in maintaining lactate production in human cancer and that the investigation of PDK-1 inhibitors should be investigated for antitumour effects.
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DOI：
10.1016/s0360-3016(01)01630-3
发表时间：
2001-10-01
影响因子：
7
作者：
Brizel, DM;Schroeder, T;Mueller-Klieser, W
通讯作者：
Mueller-Klieser, W
影响因子：
4.8
作者：
Lu, HS;Dalgard, CL;Verma, A
通讯作者：
Verma, A
DOI：
10.1073/pnas.0611662104
发表时间：
2007-05-29
影响因子：
11.1
作者：
Cairns, Rob A.;Papandreou, Ioanna;Denko, Nicholas C.
通讯作者：
Denko, Nicholas C.
影响因子：
9.7
作者：
EBOLI, ML;PASQUINI, A
通讯作者：
PASQUINI, A
影响因子：
11.2
作者：
Koukourakis, MI;Giatromanolaki, A;Sivridis, E
通讯作者：
Sivridis, E