Koval Alexey, Zhang Xin, Katanaev Vladimir L
Department of Cell Physiology and Metabolism, Translational Research Center in Oncohaematology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.
Institute of Life Sciences and Biomedicine, Far Eastern Federal University, 690922 Vladivostok, Russia.
iScience. 2023 Jul 3;26(8):107270. doi: 10.1016/j.isci.2023.107270. eCollection 2023 Aug 18.
Intracellular signaling orchestrates an organism's development and functioning and underlies various pathologies, such as cancer, when aberrant. A universal cell signaling characteristic is channel capacity - the measure of how much information a given transmitting system can reliably transduce. Here, we describe improved approaches to quantify GPCR signaling channel capacity in single cells, averaged across cell population. We assess the channel capacity based on distribution of residuals by the cellular response amplitude. We further develop means to handle irregularly responding cancer cells using the integral values of their response to different agonist concentrations. These approaches enabled us to analyze, for the first time, channel capacity in single cancer cells. A universal feature emerging for different cancer cell types is a decreased channel capacity of their GPCR signaling. These findings provide experimental validation to the hypothesis that cancer is an information disease, bearing importance for basic cancer biology and anticancer drug discovery.
细胞内信号传导协调生物体的发育和功能，并且在异常时是各种病理学（如癌症）的基础。一个普遍的细胞信号特征是通道容量——衡量给定传输系统能够可靠转导多少信息的指标。在这里，我们描述了改进的方法来量化单细胞中GPCR信号通道容量，并在细胞群体中进行平均。我们基于细胞反应幅度的残差分布来评估通道容量。我们进一步开发了利用癌细胞对不同激动剂浓度反应的积分值来处理反应不规则的癌细胞的方法。这些方法使我们首次能够分析单个癌细胞中的通道容量。不同癌细胞类型出现的一个普遍特征是其GPCR信号通道容量降低。这些发现为癌症是一种信息疾病这一假说提供了实验验证，对基础癌症生物学和抗癌药物发现具有重要意义。
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