Tumour Cell Biology Laboratory, The Francis Crick Institute, London, UK.
IEO, Istituto Europeo di Oncologia IRCCS, Milan, Italy.
Biol Cell. 2021 Apr;113(4):165-182. doi: 10.1111/boc.202000129. Epub 2020 Dec 30.
Although endocytosis was first described as the process mediating macromolecule or nutrient uptake through the plasma membrane, it is now recognised as a critical component of the cellular infrastructure involved in numerous processes, ranging from receptor signalling, proliferation and migration to polarity and stem cell regulation. To realise these varying roles, endocytosis needs to be finely regulated. Accordingly, multiple endocytic mechanisms exist that require specialised molecular machineries and an array of endocytic adaptor proteins with cell-specific functions. This review provides some examples of specialised functions of endocytic adaptors and other components of the endocytic machinery in different cell physiological processes, and how the alteration of these functions is linked to cancer. In particular, we focus on: (i) cargo selection and endocytic mechanisms linked to different adaptors; (ii) specialised functions in clathrin-mediated versus non-clathrin endocytosis; (iii) differential regulation of endocytic mechanisms by post-translational modification of endocytic proteins; (iv) cell context-dependent expression and function of endocytic proteins. As cases in point, we describe two endocytic protein families, dynamins and epsins. Finally, we discuss how dysregulation of the physiological role of these specialised endocytic proteins is exploited by cancer cells to increase cell proliferation, migration and invasion, leading to anti-apoptotic or pro-metastatic behaviours.
尽管内吞作用最初被描述为通过质膜介导大分子或营养物质摄取的过程，但现在它被认为是涉及众多过程的细胞基础设施的关键组成部分，这些过程从受体信号转导、增殖和迁移到极性和干细胞调节不等。为了实现这些不同的角色，内吞作用需要精细调节。因此，存在多种需要专门的分子机制和一系列具有细胞特异性功能的内吞衔接蛋白的内吞机制。这篇综述提供了内吞衔接蛋白和内吞机制其他成分在不同细胞生理过程中的一些特殊功能的例子，以及这些功能的改变如何与癌症相关。特别是，我们重点关注：(i)与不同衔接蛋白相关的货物选择和内吞机制；(ii)网格蛋白介导与非网格蛋白内吞作用的特殊功能；(iii)通过内吞蛋白的翻译后修饰对内吞机制的差异调节；(iv)内吞蛋白在细胞背景依赖性表达和功能。作为例子，我们描述了两个内吞蛋白家族，即动力蛋白和衔接蛋白。最后，我们讨论了这些专门的内吞蛋白的生理作用失调如何被癌细胞利用来增加细胞增殖、迁移和侵袭，导致抗凋亡或促转移行为。
