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首页> 外文期刊>Cancer and Clinical Oncology >GPCRs, at the Crossroad of Distortions in Extracellular Microenvironment and Intracellular Energetics Homeostasis, a New Model for 21st Century Cancer Therapeutics
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GPCRs, at the Crossroad of Distortions in Extracellular Microenvironment and Intracellular Energetics Homeostasis, a New Model for 21st Century Cancer Therapeutics

机译：GPCRs，在细胞外微环境和细胞内能量平衡的扭曲的十字路口，一种21世纪癌症治疗新模型

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G-protein coupled receptors (GPCRs) have evolved in complexity and are most widely used by metazoan for essential physiological functions. They are involved in mechanisms that allow cells to receive signals from their environment and react to them. Nearly 20% of human tumors harbor mutations in GPCRs and aberrant expression and activity of G proteins and G-protein-coupled receptors are frequently associated with tumorigenesis. In this article, we review and discuss the roles of GPCRs in normal and neoplastic transformation. This could be looked upon the crossroad of distortions in extracellular microenvironment and intracellular energetics landscape homeostasis. We hypothesize that GPCRs have taken over the role of sensing cellular energetics status and are involved in regulation of signal transduction and gene expression. We also present evolutionary biology perspectives lending further support to the above mentioned notions. We propose that however complex and intricate these pathways and interactions seem, they are all guided by one elegant and simple law, namely keeping the network entropy of the cell at the minimum possible level which correlates inversely with its free energy. Cancer cells are in abnormal state(s) characterized by dysregulated energetics. Based on this view of malignant transformation, further studies and measurements of cellular energetics landscape in both normal cell and its malignant counterpart and mathematical modeling could open the way for future cancer therapeutics strategies. We propose that our future cancer treatment strategies should target conversion rather than destruction of the malignant cell which is the current dominant theme of cancer therapy that has faced insurmountable barriers as evidenced by the short and limited survivorship of patients diagnosed with advanced malignant disorders.Keywords: G-protein coupled receptors, evolution, cancer, multicellular unit, environment, network entropy, free energy.
机译：G蛋白偶联受体（GPCR）的复杂性已得到发展，后生动物已将其广泛用于基本的生理功能。它们参与了使细胞从其环境接收信号并对它们做出反应的机制。近20％的人类肿瘤在GPCR中具有突变，G蛋白和G蛋白偶联受体的异常表达和活性经常与肿瘤发生有关。在本文中，我们回顾并讨论了GPCR在正常和肿瘤转化中的作用。这可以看做是细胞外微环境和细胞内高能环境动态平衡畸变的十字路口。我们假设，GPCR已取代了检测细胞能量状态的角色，并参与了信号转导和基因表达的调控。我们还提出了进化生物学的观点，这些观点进一步支持了上述观点。我们提出，不管这些途径和相互作用看起来多么复杂和复杂，它们都遵循一个优雅而简单的定律，即将细胞的网络熵保持在与其自由能成反比的最小可能水平。癌细胞处于异常状态，其特征是能量学失调。基于这种恶性转化的观点，进一步研究和测量正常细胞及其恶性对应物中的细胞能量学格局以及数学建模可以为未来的癌症治疗策略开辟道路。我们建议我们未来的癌症治疗策略应该针对转化而不是破坏恶性细胞，这是目前面临不可克服的障碍的癌症治疗的主要主题，这一点已被诊断为晚期恶性疾病的患者生存期短且有限证明了这一点。 G蛋白偶联受体，进化，癌症，多细胞单位，环境，网络熵，自由能。

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