Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
Mol Cancer. 2018 Feb 15;17(1):41. doi: 10.1186/s12943-018-0811-3.
The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. The structure of V-ATPase has been highly conserved among all eukaryotic cells and is involved in diverse functions across species. V-ATPase is best known for its acidification of endosomes and lysosomes and is also important for luminal acidification of specialized cells. Several reports have suggested the involvement of V-ATPase in maintaining an alkaline intracellular and acidic extracellular pH thereby aiding in proliferation and metastasis of cancer cells respectively. Increased expression of V-ATPase and relocation to the plasma membrane aids in cancer modulates key tumorigenic cell processes like autophagy, Warburg effect, immunomoduation, drug resistance and most importantly cancer cell signaling. In this review, we discuss the direct role of V-ATPase in acidification and indirect regulation of signaling pathways, particularly Notch Signaling.
液泡型 ATP 酶（V-ATPase）是一种质子泵，负责控制细胞内外的 pH 值。V-ATPase 的结构在所有真核细胞中都高度保守，参与了物种间的多种功能。V-ATPase 最为人所知的是其对内体和溶酶体的酸化作用，同时对专门细胞的腔内腔酸化也很重要。有几项报告表明，V-ATPase 参与维持细胞内碱性和细胞外酸性 pH 值，从而分别有助于癌细胞的增殖和转移。V-ATPase 的表达增加和向质膜的重新定位有助于癌症调节关键的致癌细胞过程，如自噬、Warburg 效应、免疫调节、耐药性，最重要的是癌细胞信号转导。在这篇综述中，我们讨论了 V-ATPase 在酸化中的直接作用以及信号通路的间接调节，特别是 Notch 信号通路。
