Thymidine phosphorylase activates NFκB and stimulates the expression of angiogenic and metastatic factors in human cancer cells.
Thymidine phosphorylase activates NFκB and stimulates the expression of angiogenic and metastatic factors in human cancer cells.
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DOI：
10.18632/oncotarget.2242
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发表时间：
2014-11-15
期刊：
影响因子：
--
通讯作者：
Akiyama S
中科院分区：
文献类型：
--
作者：
Tabata S;Ikeda R;Yamamoto M;Shimaoka S;Mukaida N;Takeda Y;Yamada K;Soga T;Furukawa T;Akiyama S
胸苷磷酸化酶 (TP) 促进血管生成和转移，并赋予某些癌细胞类型抗癌药物的抗性。我们之前报道过 TP 通过未知机制刺激人 KB 癌细胞中白细胞介素 (IL)-8 的表达。 IL-8 启动子的核因子 (NF)κB 结合位点的突变抑制了过度表达 TP 的 KB/TP 细胞中的启动子活性。使用 BY11-7082 特异性抑制 NFκB 还可抑制 TP 诱导的 IL-8 启动子活性和 IL-8 表达。此外，TP过表达导致NFκB激活及其靶基因表达上调，并增加磷酸化IKKα/β蛋白水平，同时促进IκBα降解以及p65磷酸化和核定位。 KB/TP 细胞中 NFκB 的激活被抗氧化剂 N-乙酰半胱氨酸和 EUK-8 抑制。此外，在胃癌组织样本中，NFκB调节基因（包括IL-8、IL-6和纤连蛋白-1）的表达与TP表达呈正相关。这些发现表明，TP 介导的活性氧介导的 NFκB 激活增加了促进胃癌血管生成和转移的基因的表达。
Thymidine phosphorylase (TP) promotes angiogenesis and metastasis, and confers resistance to anticancer agents in some cancer cell types. We previously reported that TP stimulates the expression of interleukin (IL)-8 in human KB cancer cells by an unknown mechanism. A mutation in the nuclear factor (NF)κB binding site of the IL-8 promoter suppressed promoter activity in KB/TP cells that overexpress TP. Specifically inhibiting NFκB by using BY11-7082 also suppressed TP-induced IL-8 promoter activity and IL-8 expression. Moreover, TP overexpression led to the activation of NFκB and an upregulation in the expression of its target genes, and increased phosphorylated IKKα/β protein levels, while promoting IκBα degradation as well as p65 phosphorylation and nuclear localization. The activation of NFκB in KB/TP cells was suppressed by the antioxidants N-acetylcysteine and EUK-8. In addition, in gastric cancer tissue samples, the expression of the NFκB-regulated genes, including IL-8, IL-6, and fibronectin-1 was positively correlated with TP expression. These findings indicate that reactive oxygen species mediated NFκB activation by TP increases the expression of genes that promote angiogenesis and metastasis in gastric cancer.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
4.8
作者：
ISHIKAWA, Y;MUKAIDA, N;MATSUSHIMA, K
通讯作者：
MATSUSHIMA, K
影响因子：
8.8
作者：
Kitadai Y;Takahashi Y;Haruma K;Naka K;Sumii K;Yokozaki H;Yasui W;Mukaida N;Ohmoto Y;Kajiyama G;Fidler IJ;Tahara E
通讯作者：
Tahara E
DOI：
10.1007/s10120-005-0315-x
发表时间：
2005-01-01
期刊：
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子：
--
作者：
Ashizawa, Tatsuto;Okada, Ryosuke;Aoki, Tatsuya
通讯作者：
Aoki, Tatsuya
DOI：
10.1016/j.bbrc.2008.03.067
发表时间：
2008-05-30
影响因子：
3.1
作者：
Ikeda, Ryuji;Tajitsu, Yusuke;Yamadaa, Katsushi
通讯作者：
Yamadaa, Katsushi