Nava Gerardo M, Madrigal Perez Luis Alberto
Universidad Autónoma de Querétaro, Cerro de las Campanas, Santiago de Querétaro, México.
Tecnológico Nacional de México/ Instituto Tecnológico Superior de Ciudad Hidalgo, Ciudad Hidalgo, México.
Expert Rev Mol Diagn. 2022 Apr;22(4):439-447. doi: 10.1080/14737159.2022.2065196. Epub 2022 Apr 12.
Adaptations of eukaryotic cells to environmental changes are important for their survival. However, under some circumstances, microenvironmental changes promote that eukaryotic cells utilize a metabolic signature resembling a unicellular organism named the Warburg effect. Most cancer cells share the Warburg effect displaying lactic fermentation and high glucose uptake. The Warburg effect also induces a metabolic rewiring stimulating glutamine consumption and lipid synthesis, also considered cancer hallmarks. Amino acid metabolism alteration due to the Warburg effect increases plasma levels of proline and branched-chain amino acids in several cancer types. Proline and lipids are probably used as electron transfer molecules in carcinogenic cells. In addition, branched-chain amino acids fuel the Krebs cycle, protein synthesis, and signaling in cancer cells.
This review covers how metabolomics studies describe changes in some metabolites and proteins associated with the Warburg effect and related metabolic pathways.
In this review, we analyze the metabolic signature of the Warburg effect and related phenotypes and propose some Warburg effect-related metabolites and proteins (lactate, glucose uptake, glucose transporters, glutamine, branched-chain amino acids, proline, and some lipogenic enzymes) as promising cancer biomarkers.
真核细胞适应环境变化对其生存至关重要。然而,在某些情况下,微环境变化促使真核细胞利用一种类似于单细胞生物的代谢特征,即瓦伯格效应。大多数癌细胞都具有瓦伯格效应,表现为乳酸发酵和高葡萄糖摄取。瓦伯格效应还会引发代谢重编程,刺激谷氨酰胺消耗和脂质合成,这也被视为癌症的标志。由于瓦伯格效应导致的氨基酸代谢改变会使多种癌症类型的血浆脯氨酸和支链氨基酸水平升高。脯氨酸和脂质可能在致癌细胞中用作电子传递分子。此外,支链氨基酸为癌细胞中的三羧酸循环、蛋白质合成和信号传导提供能量。
本综述涵盖了代谢组学研究如何描述与瓦伯格效应及相关代谢途径相关的一些代谢物和蛋白质的变化。
在本综述中,我们分析了瓦伯格效应的代谢特征及相关表型,并提出一些与瓦伯格效应相关的代谢物和蛋白质(乳酸、葡萄糖摄取、葡萄糖转运蛋白、谷氨酰胺、支链氨基酸、脯氨酸和一些脂肪生成酶)作为有前景的癌症生物标志物。