Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, A-8036 Graz, Austria.
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, A-8036 Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, A-8010 Graz, Austria.
Biochim Biophys Acta Rev Cancer. 2019 Aug;1872(1):24-36. doi: 10.1016/j.bbcan.2019.05.006. Epub 2019 May 30.
Cancer cells constantly face a fluctuating nutrient supply and interference with adaptive responses might be an effective therapeutic approach. It has been discovered that in the absence of glucose, cancer cells can synthesize crucial metabolites by expressing phosphoenolpyruvate carboxykinase (PEPCK, PCK1 or PCK2) using abbreviated forms of gluconeogenesis. Gluconeogenesis, which in essence is the reverse pathway of glycolysis, uses lactate or amino acids to feed biosynthetic pathways branching from glycolysis. PCK1 and PCK2 have been shown to be critical for the growth of certain cancers. In contrast, fructose-1,6-bisphosphatase 1 (FBP1), a downstream gluconeogenesis enzyme, inhibits glycolysis and tumor growth, partly by non-enzymatic mechanisms. This review sheds light on the current knowledge of cancer cell gluconeogenesis and its role in metabolic reprogramming, cancer cell plasticity, and tumor growth.
癌细胞不断面临着波动的营养供应，干扰适应性反应可能是一种有效的治疗方法。已经发现，在没有葡萄糖的情况下，癌细胞可以通过表达磷酸烯醇丙酮酸羧激酶（PEPCK、PCK1 或 PCK2），使用糖异生的缩写形式来合成关键代谢物。糖异生本质上是糖酵解的逆途径，利用乳酸盐或氨基酸来为糖酵解分支的生物合成途径提供养分。已经表明 PCK1 和 PCK2 对某些癌症的生长至关重要。相比之下，果糖-1,6-二磷酸酶 1（FBP1），一种下游糖异生酶，通过非酶机制抑制糖酵解和肿瘤生长，部分是通过非酶机制。这篇综述阐明了癌细胞糖异生及其在代谢重编程、癌细胞可塑性和肿瘤生长中的作用的现有知识。
