Distinct growth factor-induced dynamic mass redistribution (DMR) profiles for monitoring oncogenic signaling pathways in various cancer cells.
Distinct growth factor-induced dynamic mass redistribution (DMR) profiles for monitoring oncogenic signaling pathways in various cancer cells.
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DOI：
10.1080/10799890902976933
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Fu H
中科院分区：
文献类型：
--
作者：
Du Y;Li Z;Li L;Chen ZG;Sun SY;Chen P;Shin DM;Khuri FR;Fu H
靶向肿瘤中失调的信号通路导致了一类新型信号转导抑制剂的发展，包括表皮生长因子（EGF）受体（EGFR）抑制剂。为了剖析致癌途径，确定关键途径决定因素，并评估靶向药物的疗效，开发能够检测生理条件下时间信号事件的技术至关重要。在这里，我们报告了一种无标记光学生物传感器的应用，以揭示癌细胞对EGF的快速反应，表达为动态质量再分配（DMR）信号。在对EGF的反应中，头颈部细胞的鳞状细胞癌表现出DMR信号的快速上升，而肺腺癌细胞表现出双相的DMR特征，表明细胞类型依赖性的DMR反应。药理学研究表明，EGFR和磷脂酰肌醇-3激酶途径在介导egf诱导的DMR反应中的重要性。定义的DMR特征为评估egfr靶向药物提供了一种简单而敏感的工具，如吉非替尼和厄洛替尼所示。该检测还可用于基于细胞的EGF通路抑制剂的高通量筛选，其在384孔板格式（Z ' > 0.5）中具有强大的性能。该技术适用于其他致癌途径，用于发现治疗各种癌症的新型治疗剂。
Targeting dysregulated signaling pathways in tumors has led to the development of a novel class of signal transduction inhibitors, including inhibitors of the epidermal growth factor (EGF) receptor (EGFR). To dissect oncogenic pathways, identify key pathway determinants, and evaluate the efficacy of targeted agents, it is vital to develop technologies that allow the detection of temporal signaling events under physiological conditions. Here we report the application of a label-free optical biosensor to reveal the rapid response of cancer cells to EGF, expressed as a dynamic mass redistribution (DMR) signal. In response to EGF, squamous cell carcinoma of the head and neck cells exhibited a rapid rise in DMR signal, whereas lung adenocarcinoma cells showed a biphasic DMR profile, suggesting a cell type-dependent DMR response. Pharmacological studies suggested the importance of EGFR and the phosphatidylinositol-3 kinase pathway in mediating the EGF-induced DMR response. The defined DMR signatures offer a simple yet sensitive tool for evaluating EGFR-targeted agents, as shown with gefitinib and erlotinib. The assay can also be used for cell-based high-throughput screening of EGF pathway inhibitors, as demonstrated by its robust performance in a 384-well plate format (Z′ > 0.5). This technology is applicable to other oncogenic pathways for the discovery of novel therapeutic agents for the treatment of various cancers.
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影响因子：
3.4
作者：
Fang, Ye;Ferrie, Ann M.;Balakrishnan, Jitendra
通讯作者：
Balakrishnan, Jitendra
DOI：
10.1016/j.ijrobp.2003.09.099
发表时间：
2004-03-01
影响因子：
7
作者：
Langer, CJ
通讯作者：
Langer, CJ
影响因子：
6.2
作者：
Muller, Susan;Su, Ling;(Georgia) Chen, Zhuo
通讯作者：
(Georgia) Chen, Zhuo
影响因子：
--
作者：
Sattler M;Abidoye O;Salgia R
通讯作者：
Salgia R
影响因子：
10.3
作者：
Grandis, JR;Melhem, MF;Tweardy, DJ
通讯作者：
Tweardy, DJ