Galenkamp Koen M O, Commisso Cosimo
Cell and Molecular Biology of Cancer Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
Front Cell Dev Biol. 2021 May 13;9:664295. doi: 10.3389/fcell.2021.664295. eCollection 2021.
Cancer cells exhibit increased glycolytic flux and adenosine triphosphate (ATP) hydrolysis. These processes increase the acidic burden on the cells through the production of lactate and protons. Nonetheless, cancer cells can maintain an alkaline intracellular pH (pHi) relative to untransformed cells, which sets the stage for optimal functioning of glycolytic enzymes, evasion of cell death, and increased proliferation and motility. Upregulation of plasma membrane transporters allows for H and lactate efflux; however, recent evidence suggests that the acidification of organelles can contribute to maintenance of an alkaline cytosol in cancer cells by siphoning off protons, thereby supporting tumor growth. The Golgi is such an acidic organelle, with resting pH ranging from 6.0 to 6.7. Here, we posit that the Golgi represents a "proton sink" in cancer and delineate the proton channels involved in Golgi acidification and the ion channels that influence this process. Furthermore, we discuss ion channel regulators that can affect Golgi pH and Golgi-dependent processes that may contribute to pHi homeostasis in cancer.
癌细胞表现出糖酵解通量增加和三磷酸腺苷（ATP）水解增加。这些过程通过乳酸和质子的产生增加了细胞的酸性负担。尽管如此，相对于未转化的细胞，癌细胞可以维持碱性的细胞内pH值（pHi），这为糖酵解酶的最佳功能、逃避细胞死亡以及增加增殖和运动性奠定了基础。质膜转运体的上调允许氢离子和乳酸外流；然而，最近的证据表明，细胞器的酸化可以通过吸除质子来促进癌细胞中碱性细胞质溶胶的维持，从而支持肿瘤生长。高尔基体就是这样一个酸性细胞器，其静息pH值范围为6.0至6.7。在此，我们认为高尔基体在癌症中代表一个“质子汇”，并描述参与高尔基体酸化的质子通道以及影响这一过程的离子通道。此外，我们讨论了可以影响高尔基体pH值的离子通道调节剂以及可能有助于癌症中pHi稳态的高尔基体依赖性过程。
