Khakwani Muhammad Mahtab Aslam Khan, Ji Xin-Ying, Khattak Saadullah, Sun Ying-Chuan, Yao Kunhou, Zhang Lei
Department of General Surgery, Huaihe Hospital of Henan University, Henan University, Kaifeng 475004, China; Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medicine, Henan University, Kaifeng, Henan 475004, China.
Department of Oncology, Huaxian County Hospital, Huaxian, Henan Province 456400, China; Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Gong-Ming Rd, Mazhai Town, Erqi District, Zhengzhou, Henan 450064, China.
J Adv Res. 2025 Apr;70:423-444. doi: 10.1016/j.jare.2024.06.009. Epub 2024 Jun 13.
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.
核孔复合体（NPCs）是细胞内核膜中固有的结构，可调节蛋白质和RNA等物质的核质运输，以确保细胞正常运作。蛋白质和RNA在细胞内的正确定位对其正常功能至关重要。对于物质通过NPC的如此复杂的运输过程，约60种蛋白质参与其中，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、货物跨NPC转运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的结构和功能常常会因核孔蛋白和核转运蛋白的表达改变而被夸大，进而影响相关信号通路中的其他蛋白质。目前，一些核转运蛋白抑制剂有潜力调节这些核转运蛋白分子的改变水平/表达。
本综述总结了1990年至2023年的数据，主要关注近期研究，这些研究阐述了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及机制，以及治疗价值，以便了解与NPC相关的结直肠癌的病理和潜在基础。据我们所知，这是第一篇阐明针对NPC处结直肠癌的详细最新研究的综述。该综述还旨在将某些核转运蛋白、核孔蛋白及其可能的抑制剂和激活剂分子作为治疗策略。
NPC结构有助于理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质运输。许多研究提供了证据，描述了核孔蛋白和核转运蛋白的破坏不仅在结直肠癌中，而且在其他非血液学和血液学恶性肿瘤中的作用。目前，一些核转运蛋白抑制剂对结直肠癌具有治疗潜力，然而，开发更有效的抑制剂可能在不久的将来为结直肠癌提供更有效的治疗策略。
