SCI

5 June 2023

Endocytosis in cancer and cancer therapy

（nature reviews cancer; IF: 69.800）

Blerida Banushi, Shannon R. Joseph, Benedict Lum, Jason J. Lee Abstract & Fiona Simpson 

CORRESPONDENCE TO: f.simpson@uq.edu.au 

Endocytosis is a complex process whereby cell surface proteins, lipids and fluid from the extracellular environment are packaged, sorted and internalized into cells. Endocytosis is also a mechanism of drug internalization into cells. There are multiple routes of endocytosis that determine the fate of molecules, from degradation in the lysosomes to recycling back to the plasma membrane. The overall rates of endocytosis and temporal regulation of molecules transiting through endocytic pathways are also intricately linked with signalling outcomes. This process relies on an array of factors, such as intrinsic amino acid motifs and post-translational modifications. Endocytosis is frequently disrupted in cancer. These disruptions lead to inappropriate retention of receptor tyrosine kinases on the tumour cell membrane, changes in the recycling of oncogenic molecules, defective signalling feedback loops and loss of cell polarity. In the past decade, endocytosis has emerged as a pivotal regulator of nutrient scavenging, response to and regulation of immune surveillance and tumour immune evasion, tumour metastasis and therapeutic drug delivery. This Review summarizes and integrates these advances into the understanding of endocytosis in cancer. The potential to regulate these pathways in the clinic to improve cancer therapy is also discussed.

细胞内吞是一个复杂的过程，来自细胞外环境的细胞表面蛋白质、脂质和液体被包装、分类并内化为细胞。内吞作用也是药物内化进入细胞的一种机制。内吞作用有多种途径，决定了分子的命运，从在溶酶体中降解到回收到质膜上。内吞作用的总体速率和通过内吞途径转运的分子的时间调控也与信号结果有着复杂的联系。这一过程依赖于一系列的因素，如内在的氨基酸主题和翻译后的修饰。内吞作用在癌症中经常被破坏。这些破坏导致受体酪氨酸激酶在肿瘤细胞膜上的不适当保留，致癌分子循环的变化，信号反馈回路的缺陷和细胞极性的丧失。在过去十年中，内吞作用已经成为营养物质清除、对免疫监视和肿瘤免疫逃避的反应和调节、肿瘤转移和治疗性药物输送的关键调节因素。本文总结并整合了这些进展，以了解癌症中的内吞作用，并讨论了在临床上调节这些途径以改善癌症治疗的潜力。

来源 | 健康界

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