Nuclear pore complexes (NPCs) are the architectures entrenched in nuclear envelop of a cell that regulate the nucleo-cytoplasmic transportation of materials, such as proteins and RNAs for proper functioning of a cell. The appropriate localization of proteins and RNAs within the cell is essential for its normal functionality. For such a complex transportation of materials across the NPC, around 60 proteins are involved comprising nucleoporins, karyopherins and RAN system proteins that play a vital role in NPC’s structure formation, cargo translocation across NPC, and cargoes’ rapid directed transportation respectively. In various cancers, the structure and function of NPC is often exaggerated, following altered expressions of its nucleoporins and karyopherins, affecting other proteins of associated signaling pathways. Some inhibitors of karyopherins at present, have potential to regulate the altered level/expression of these karyopherin molecules. This review summarizes the data from 1990 to 2023, mainly focusing on recent studies that illustrate the structure and function of NPC, the relationship and mechanisms of nucleoporins and karyopherins with colorectal cancer, as well as therapeutic values, in order to understand the pathology and underlying basis of colorectal cancer associated with NPC. This is the first review to our knowledge elucidating the detailed updated studies targeting colorectal cancer at NPC. The review also aims to target certain karyopherins, Nups and their possible inhibitors and activators molecules as a therapeutic strategy. NPC structure provides understanding, how nucleoporins and karyopherins as key molecules are responsible for appropriate nucleocytoplasmic transportation. Many studies provide evidences, describing the role of disrupted nucleoporins and karyopherins not only in CRC but also in other non-hematological and hematological malignancies. At present, some inhibitors of karyopherins have therapeutic potential for CRC, however development of more potent inhibitors may provide more effective therapeutic strategies for CRC in near future.

中文翻译：

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在核孔复合物水平靶向结直肠癌


核孔复合体 (NPC) 是根植于细胞核被膜中的结构，可调节蛋白质和 RNA 等物质的核质运输，以保证细胞的正常功能。蛋白质和 RNA 在细胞内的适当定位对其正常功能至关重要。对于如此复杂的穿过 NPC 的物质运输，涉及约 60 种蛋白质，包括核孔蛋白、核转运蛋白和 RAN 系统蛋白，它们分别在 NPC 的结构形成、穿过 NPC 的货物易位以及货物的快速定向运输中发挥着至关重要的作用。在各种癌症中，NPC 的结构和功能经常被夸大，因为其核孔蛋白和核转运蛋白的表达发生改变，从而影响相关信号传导途径的其他蛋白质。目前，一些核传递蛋白抑制剂有可能调节这些核传递蛋白分子的水平/表达的改变。本综述总结了1990年至2023年的资料，主要集中阐述近年来NPC的结构和功能、核孔蛋白和核转运蛋白与结直肠癌的关系和机制以及治疗价值的研究，以了解其病理学和潜在的作用。结直肠癌与鼻咽癌相关的基础。据我们所知，这是首次综述，阐明 NPC 针对结直肠癌的详细最新研究。该综述还旨在针对某些核转运蛋白、Nups 及其可能的抑制剂和激活剂分子作为治疗策略。 NPC 结构让我们了解核孔蛋白和核转运蛋白作为关键分子如何负责适当的核细胞质运输。 许多研究提供了证据，描述了破坏的核孔蛋白和核传递蛋白不仅在结直肠癌中而且在其他非血液和血液恶性肿瘤中的作用。目前，一些核转运蛋白抑制剂具有治疗结直肠癌的潜力，然而，开发更有效的抑制剂可能会在不久的将来为结直肠癌提供更有效的治疗策略。