Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer.
Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer.
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DOI：
10.3390/ijms18010189
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发表时间：
2017-01-18
影响因子：
5.6
通讯作者：
Antonescu CN
中科院分区：
文献类型：
--
作者：
Ata R;Antonescu CN
整合素是细胞存活、增殖、粘附和迁移的重要调节因子。一旦被激活，整合素在细胞外基质和细胞骨架之间建立了一个受调节的联系。整合素在癌症中的作用已被证实，例如通过参与许多特定的细胞内信号通路来控制细胞存活和促进转移。整合素和相关蛋白通过转录、膜传输和降解的控制以及一系列翻译后修饰（包括糖基化）来调节，从而调节整合素的功能以适应各种细胞需要和环境条件。在这篇综述中，我们研究了细胞代谢对整合素功能的控制，以及这种调节在癌症中的影响。在这种情况下，营养充足或缺乏是由许多代谢信号通路感知的，如amp活化蛋白激酶（AMPK）、哺乳动物雷帕霉素靶蛋白（mTOR）和缺氧诱导因子（HIF） 1，它们通过多种机制共同控制整合素的功能。此外，通过特定途径的代谢通量也控制整合素，例如通过控制整合素糖基化，从而影响整合素依赖性细胞的粘附和迁移。整合素还控制各种代谢信号和途径，建立了这种调节的互惠性。随着癌细胞代谢发生实质性变化，如向有氧糖酵解转变，葡萄糖利用增强，对特定氨基酸的依赖性增强，整合素和代谢的相互调节可能为更有效地治疗各种癌症提供重要线索。
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions. In this review, we examine the control of integrin function by cell metabolism, and the impact of this regulation in cancer. Within this context, nutrient sufficiency or deprivation is sensed by a number of metabolic signaling pathways such as AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) 1, which collectively control integrin function by a number of mechanisms. Moreover, metabolic flux through specific pathways also controls integrins, such as by control of integrin glycosylation, thus impacting integrin-dependent cell adhesion and migration. Integrins also control various metabolic signals and pathways, establishing the reciprocity of this regulation. As cancer cells exhibit substantial changes in metabolism, such as a shift to aerobic glycolysis, enhanced glucose utilization and a heightened dependence on specific amino acids, the reciprocal regulation of integrins and metabolism may provide important clues for more effective treatment of various cancers.