溶酶体V-ATPase调节肿瘤的pH稳态

Lysosomal V-ATPase Regulates pH Homeostasis in Tumors

摘要: 癌细胞产生大量的细胞质质子，作为异常激活的有氧糖酵解和乳酸发酵的副产物。为了避免细胞内酸化的不利影响，癌细胞激活了促进胞内碱化和胞外酸化的质子清除途径。越来越多的证据表明，除了质膜中一些特殊的离子泵和转运蛋白外，癌细胞溶酶体为此发生重新编程。溶酶体膜上的液泡型H –三磷酸腺苷酶(V-ATPase)的表达和活性增加，且伴随溶酶体体积的增大，大大增加了溶酶体的质子存储能力，从而维持pH梯度逆转，促进癌细胞的生存和生长。本文主要对肿瘤细胞中的溶酶体V-ATPase的作用进行综述。

Abstract: Cancer cells generate large quantities of cytoplasmic protons as byproducts of aberrantly activated aerobic glycolysis and lactate fermentation. To avoid the adverse effects of intracellular acidification, cancer cells activate multiple acid-removal pathways that promote cytosolic to the alkalization and extracellular acidification. Accumulating evidence suggests that in addition to the ion pumps and exchangers in the plasma membrane, cancer cell lysosomes are also reprogrammed for this purpose. The increased expression and activity of the vacuolar-type H -ATPase (V-ATPase) on the lysosomal limiting membrane combined with the larger volume of the lysosomal compartment increases the lysosomal proton storage capacity substantially, thereby maintaining the reversal of pH gradient and promoting the survival and growth of cancer cells. This review focuses on the role of lysosomal V-ATPase in tumor cells.