Grimm Christian, Bartel Karin, Vollmar Angelika M, Biel Martin
Munich Center for Integrated Protein Science CIPSM, 81377 München, Germany.
Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, 81377 München, Germany.
Pharmaceuticals (Basel). 2018 Jan 5;11(1):4. doi: 10.3390/ph11010004.
The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells.
内溶酶体系统（ES）由溶酶体、早期、晚期和再循环内体以及自噬体组成。它不仅是大分子降解与再循环、质膜修复、体内平衡和脂质储存的关键调节因子，也是抗原呈递、免疫防御、细胞运动、细胞死亡信号传导、肿瘤生长和癌症进展的关键调节因子。此外，它在自噬中起关键作用，自噬 - 溶酶体途径与癌症的特征密切相关，如逃避细胞死亡途径、逃避免疫监视和代谢失调。内溶酶体的功能严重依赖于可溶性和内溶酶体膜蛋白，如离子通道和转运蛋白。在内溶酶体系统中发现的阳离子通道包括瞬时受体电位（TRP）通道超家族的成员，即TRPML通道（黏脂蛋白）以及双孔通道（TPC）。在最近的研究中，已发现这些通道在内溶酶体运输、溶酶体胞吐作用和自噬中起关键作用。这些通道蛋白的突变或缺失会影响多种内溶酶体运输途径。最近已确定TPC在癌细胞迁移和转移中的作用，这与内溶酶体运输中的不同缺陷（如整合素运输）有关。在本综述中，我们概述了溶酶体在癌症中的功能，特别关注TPC和TRPML通道在内溶酶体系统中所起的作用以及这如何影响癌细胞。
