背景:核孔复合物(NPC)是细胞的核包膜中根深蒂固的结构,其调节诸如蛋白质和RNA的物质的核-细胞质运输以使细胞正常运作。蛋白质和RNA在细胞内的适当定位对于其正常功能至关重要。对于如此复杂的跨越NPC的材料运输,大约有60种蛋白质参与其中,包括核孔蛋白,在NPC的结构形成中起重要作用的核动力蛋白和RAN系统蛋白,跨NPC的货物转运,和货物分别是快速定向运输。在各种癌症中,NPC的结构和功能经常被夸大,在其核孔蛋白和核动力蛋白的表达改变后,影响相关信号通路的其他蛋白质。目前的一些核调素抑制剂具有调节这些核调素分子的改变的水平/表达的潜力。
目的:这篇综述总结了1990年至2023年的数据,主要集中在说明NPC结构和功能的最新研究,核孔蛋白和核蛋白与结直肠癌的关系和机制,以及治疗价值,为了了解与NPC相关的结直肠癌的病理和基础。这是我们知识的第一次综述,阐明了针对NPC结直肠癌的详细更新研究。该审查还旨在针对某些核动力蛋白,Nups及其可能的抑制剂和激活剂分子作为治疗策略。
■NPC结构提供了理解,作为关键分子的核孔蛋白和核蛋白如何负责适当的核质运输。许多研究提供了描述破坏的核孔蛋白和核动力蛋白不仅在CRC中而且在其他非血液和血液恶性肿瘤中的作用的证据。目前,一些核蛋白抑制剂对CRC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CRC提供更有效的治疗策略.
BACKGROUND: 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.
OBJECTIVE: 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.
UNASSIGNED: 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.