Engedal Nikolai, Mills Ian G
Prostate Cancer Research Group, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.
Prostate Cancer Research Group, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway; Department of Cancer Prevention, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Urology, Oslo University Hospital, Oslo, Norway; Uro-Oncology Research Group, Cambridge Research Institute, University of Cambridge, Cambridge, United Kingdom.
Methods Enzymol. 2014;535:179-200. doi: 10.1016/B978-0-12-397925-4.00012-2.
The endosomal system provides a route whereby nutrients, viruses, and receptors are internalized. During the course of endocytosis, activated receptors can accumulate within endosomal structures and certain signal-transducing molecules can be recruited to endosomal membranes. In the context of signaling and cancer, they provide platforms within the cell from which signals can be potentiated or attenuated. Regulation of the duration of receptor signaling is a pivotal means of refining growth responses in cells. In cancers, this is often considered in terms of mutations that affect receptor tyrosine kinases and maintain them in hyperactivated states of dimerization and/or phosphorylation. However, disruption to the regulatory control exerted by the assembly of protein complexes within the endosomal network can also contribute to disease among which oncogenesis is characterized in part by dysregulated growth, enhanced cell survival, and changes in the expression of markers of differentiation. In this chapter, we will discuss the role of proteins that regulate in endocytosis as tumor suppressors or oncogenes and how changing the fate of internalized receptors and concomitant endosomal signaling can contribute to cancer.
内体系统提供了一条使营养物质、病毒和受体得以内化的途径。在胞吞作用过程中，活化的受体可在内体结构中积累，某些信号转导分子可被招募至内体膜。在信号传导和癌症的背景下，它们在细胞内提供了可增强或减弱信号的平台。受体信号传导持续时间的调节是优化细胞生长反应的关键手段。在癌症中，这通常被认为是影响受体酪氨酸激酶并使其维持在二聚化和/或磷酸化的过度激活状态的突变。然而，内体网络中蛋白质复合物组装所施加的调节控制的破坏也可导致疾病，其中肿瘤发生部分特征为生长失调、细胞存活增强以及分化标志物表达的变化。在本章中，我们将讨论调节内吞作用的蛋白质作为肿瘤抑制因子或癌基因的作用，以及改变内化受体的命运和伴随的内体信号传导如何导致癌症。
