Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer.
Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer.
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DOI：
10.1002/ijc.24835
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发表时间：
2010-03-15
影响因子：
6.4
通讯作者：
Koenigsrainer, Alfred
中科院分区：
文献类型：
--
作者：
Zieker, Derek;Koenigsrainer, Ingmar;Tritschler, Isabel;Loeffler, Markus;Beckert, Stefan;Traub, Frank;Nieselt, Kay;Buehler, Sarah;Weller, Michael;Gaedcke, Jochen;Taichman, Russell S.;Northoff, Hinnak;Bruecher, Bjoern L. D. M.;Koenigsrainer, Alfred
腹膜癌病是胃癌的常见发现，与预后不良相关。迄今为止，人们对胃肿瘤扩散的特征知之甚少。此前，我们发现腹膜癌病胃癌患者的标本中，磷酸甘油酸激酶1（PGK1）（糖酵解途径中的一种ATP生成酶）、趋化因子受体4（CXCR4）、相应的趋化因子配体12（CXCL12）和β-连环蛋白的mRNA水平升高。在这项研究中，评估了 PGK1 对 CXCR4 和 β-catenin 的影响以及 PGK1 过表达癌细胞的侵袭性。在当前的研究中，我们发现 PGK1 在 mRNA 和蛋白质水平上调节 CXCR4 和 β-catenin 的表达。另一方面，CXCR4调节PGK1的表达。质粒介导的 PGK1 过度表达显着增加了胃癌细胞的侵袭性。有趣的是，在过度表达 PGK1 的细胞中抑制 CXCR4 仅产生适度的侵袭性降低，表明 PGK1 本身在肿瘤侵袭性中具有关键作用。弥漫性胃癌患者标本的免疫组织化学也显示，腹膜癌病患者中 PGK1 过度表达。因此，PGK1可能是腹膜传播中的关键酶。这些研究结果表明，胃癌细胞中 PGK1 及其信号传导靶标 CXCR4 和 β-catenin 表达的增强可促进腹膜癌病。因此，PGK1可以作为预后标志物和/或作为防止胃癌细胞扩散到腹膜的潜在治疗靶点。
Peritoneal carcinomatosis is a frequent finding in gastric cancer associated with a poor prognosis. The features that enable gastric tumors to disseminate are poorly understood until now. Previously, we showed elevated mRNA levels of phosphoglycerate kinase 1 (PGK1), an ATP-generating enzyme in the glycolytic pathway, the chemokine receptor 4 (CXCR4), the corresponding chemokine ligand 12 (CXCL12) and β-catenin in specimens from gastric cancer patients with peritoneal carcinomatosis. In this study the influence of PGK1 on CXCR4 and β-catenin was assessed as well as the invasiveness of PGK1 overexpressing cancer cells. In this current study we found that PGK1 regulates the expression of CXCR4 and β-catenin at the mRNA and protein levels. On the other hand, CXCR4 regulates the expression of PGK1. Plasmid-mediated overexpression of PGK1 dramatically increased the invasiveness of gastric cancer cells. Interestingly, inhibition of CXCR4 in cells overexpressing PGK1 produced only a moderate reduction of invasiveness, suggesting that PGK1 itself has a critical role in tumor invasiveness. Immunohistochemistry in specimens from diffuse gastric cancer patients also revealed an overexpression of PGK1 in patients with development of peritoneal carcinomatosis. Therefore, PGK1 may be a crucial enzyme in peritoneal dissemination. Together these findings suggest that the enhanced expression of PGK1 and its signaling targets CXCR4 and β-catenin in gastric cancer cells promote peritoneal carcinomatosis. Thus, PGK1 may serve as prognostic marker and/or be a potential therapeutic target to prevent dissemination of gastric carcinoma cells into the peritoneum.
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影响因子：
29.4
作者：
Saur, D;Seidler, B;Schmid, RM
通讯作者：
Schmid, RM
DOI：
10.1016/j.bbamcr.2003.11.004
发表时间：
2004-04-01
影响因子：
5.1
作者：
Daly, EB;Wind, T;Hogg, PJ
通讯作者：
Hogg, PJ
影响因子：
20.3
作者：
Dunussi-Joannopoulos, K;Zuberek, K;Leonard, JP
通讯作者：
Leonard, JP
影响因子：
3.8
作者：
Mosadegh, Bobak;Saadi, Wajeeh;Jeon, Noo Li
通讯作者：
Jeon, Noo Li
影响因子：
7
作者：
Zhang, DH;Tai, LK;Koay, ESC
通讯作者：
Koay, ESC