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胆碱激酶作为连接磷脂代谢与细胞周期调控的纽带:对癌症治疗的启示

Choline kinase as a link connecting phospholipid metabolism and cell cycle regulation: implications in cancer therapy.

作者信息

Ramírez de Molina Ana, Gallego-Ortega David, Sarmentero-Estrada Jacinto, Lagares David, Gómez Del Pulgar Teresa, Bandrés Eva, García-Foncillas Jesús, Lacal Juan Carlos

机构信息

Translational Oncology Unit CSIC-UAM-La Paz, Centro Nacional de Biotecnología (CNB), Darwin 3, 28049 Madrid, Spain.

出版信息

Int J Biochem Cell Biol. 2008;40(9):1753-63. doi: 10.1016/j.biocel.2008.01.013. Epub 2008 Jan 19.

Abstract

Choline kinase alpha (ChoKalpha) is an enzyme involved in the metabolism of phospholipids recently found to play a relevant role in the regulation of cell proliferation, oncogenic transformation and human carcinogenesis. In addition, this novel oncogene has been recently defined as a prognostic factor in human cancer, and as a promising target for therapy since its specific inhibitors display efficient antitumoral activity in vivo. However, the mechanism by which this enzyme is involved in the regulation of these processes is not yet understood. Using differential microarray analysis, we identify target genes that provide the basis for the understanding of the molecular mechanism for the regulation of cell proliferation and transformation mediated by over-expression of the human ChoKalpha. These results fully support a critical role of this enzyme in the regulation of the G1-->S transition at different levels, and its relevant role in human carcinogenesis. The molecular basis to understand the connection between phospholipids metabolism and cell cycle regulation through choline kinase is reported.

摘要

胆碱激酶α(ChoKα)是一种参与磷脂代谢的酶,最近发现它在细胞增殖、致癌转化和人类癌症发生的调控中发挥着重要作用。此外,这种新型癌基因最近被定义为人类癌症的一个预后因素,并且由于其特异性抑制剂在体内显示出有效的抗肿瘤活性,它还是一个有前景的治疗靶点。然而,该酶参与这些过程调控的机制尚不清楚。通过差异微阵列分析,我们鉴定出了一些靶基因,这些基因为理解由人类ChoKα过表达介导的细胞增殖和转化调控的分子机制提供了基础。这些结果充分支持了该酶在不同水平上调控G1期向S期转变中的关键作用,以及它在人类癌症发生中的重要作用。本文报道了通过胆碱激酶理解磷脂代谢与细胞周期调控之间联系的分子基础。

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