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Pin1作为癌症治疗靶点的作用机制。

The mechanisms of Pin1 as targets for cancer therapy.

作者信息

Liu Chuanfeng, Dan Lingying, Li Quan, Bajinka Ousman, Yuan Xingxing

机构信息

Department of Pulmonary and Critical Care Medicine, Lishui Hospital of Traditional Chinese Medicine, Lishui, China.

Department of Endocrinology, Lishui Hospital of Traditional Chinese Medicine, Lishui, China.

出版信息

Front Immunol. 2024 Nov 18;15:1482088. doi: 10.3389/fimmu.2024.1482088. eCollection 2024.

DOI:10.3389/fimmu.2024.1482088
PMID:39624096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11609185/
Abstract

Targeted therapy has considerable promise for the effective eradication of cancer at the primary tumor site prior to subsequent metastasis. Using this therapeutic approach, gaining an understanding of mechanistic cancer models is essential for facilitating the inhibition or suppression of tumor growth. Among different oncogenes and proteins, the protein interacting with never-in-mitosis kinase-1 (Pin1) is particularly important. The interaction between Pin1 and phosphorylated threonine-proline motifs results in significant alterations in protein structure and function. In this review, we provide a comprehensive summary of the processes involving Pin1 and its mechanisms in the context of cancer therapy. Pin1 enhances signaling pathways in a number of different human cancers and plays a pivotal role in the suppressive mechanisms relevant to cancer treatment. It is essential for the regulation of proline-directed phosphorylation and for modulating tumor suppressors. Inhibitors of Pin1, particularly naturally occurring substances, have been found to inhibit the carcinogenic activity of Pin1, and consequently this protein could represent an excellent candidate for novel cancer treatment strategies, offering a valuable therapeutic target in carcinogenesis and treatment resistance.

摘要

靶向治疗对于在后续转移之前有效根除原发性肿瘤部位的癌症具有相当大的前景。采用这种治疗方法时,了解机制性癌症模型对于促进肿瘤生长的抑制至关重要。在不同的癌基因和蛋白质中,与有丝分裂阻滞缺陷蛋白1(Pin1)相互作用的蛋白质尤为重要。Pin1与磷酸化苏氨酸 - 脯氨酸基序之间的相互作用导致蛋白质结构和功能发生显著改变。在本综述中,我们全面总结了在癌症治疗背景下涉及Pin1的过程及其机制。Pin1在多种不同的人类癌症中增强信号通路,并在与癌症治疗相关的抑制机制中起关键作用。它对于脯氨酸定向磷酸化的调节和肿瘤抑制因子的调节至关重要。已发现Pin1抑制剂,特别是天然存在的物质,可抑制Pin1的致癌活性,因此这种蛋白质可能是新型癌症治疗策略的极佳候选物,在致癌作用和治疗抗性方面提供了有价值的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe69/11609185/19c85b689daa/fimmu-15-1482088-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe69/11609185/9f13303fa299/fimmu-15-1482088-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe69/11609185/19c85b689daa/fimmu-15-1482088-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe69/11609185/9f13303fa299/fimmu-15-1482088-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe69/11609185/19c85b689daa/fimmu-15-1482088-g002.jpg

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本文引用的文献

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Impact of Juglone, a PIN1 İnhibitor, on Oral Carcinogenesis Induced by 4-Nitroquinoline-1-Oxide (4NQO) in Rat Model.胡桃醌,一种 PIN1 抑制剂,对 4-硝基喹啉 1-氧化物(4NQO)诱导的大鼠口腔癌变的影响。
Medicina (Kaunas). 2024 Jul 23;60(8):1192. doi: 10.3390/medicina60081192.
2
The role of the master cancer regulator Pin1 in the development and treatment of cancer.主要癌症调控因子Pin1在癌症发生发展及治疗中的作用。
Front Cell Dev Biol. 2024 Apr 30;12:1343938. doi: 10.3389/fcell.2024.1343938. eCollection 2024.
3
PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2.
PIN1 通过 RACK1 介导的 ANXA2 磷酸化促进胆管癌细胞的转移。
Cell Oncol (Dordr). 2024 Aug;47(4):1233-1252. doi: 10.1007/s13402-024-00924-y. Epub 2024 Feb 22.
4
Molecular docking, 3D-QASR and molecular dynamics simulations of benzimidazole Pin1 inhibitors.苯并咪唑类 Pin1 抑制剂的分子对接、3D-QASR 和分子动力学模拟。
Phys Chem Chem Phys. 2024 Jan 31;26(5):4643-4656. doi: 10.1039/d3cp05658a.
5
Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells.USP34 通过稳定 Pin1 促进 Ubc9 异构化和胶质瘤干细胞中的蛋白质 SUMO 化。
Nat Commun. 2024 Jan 2;15(1):40. doi: 10.1038/s41467-023-44349-x.
6
PIN1P1 is activated by CREB1 and promotes gastric cancer progression via interacting with YBX1 and upregulating PIN1.PIN1P1 通过与 YBX1 相互作用并上调 PIN1 被 CREB1 激活,从而促进胃癌的进展。
J Cell Mol Med. 2024 Jan;28(1):e18022. doi: 10.1111/jcmm.18022. Epub 2023 Nov 6.
7
Biological Function of Pin1 in Vivo and Its Inhibitors for Preclinical Study: Early Development, Current Strategies, and Future Directions.Pin1 在体内的生物学功能及其抑制剂用于临床前研究:早期发展、当前策略和未来方向。
J Med Chem. 2023 Jul 27;66(14):9251-9277. doi: 10.1021/acs.jmedchem.3c00390. Epub 2023 Jul 12.
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Targeting CDK1 in cancer: mechanisms and implications.靶向癌症中的细胞周期蛋白依赖性激酶1:机制与意义
NPJ Precis Oncol. 2023 Jun 13;7(1):58. doi: 10.1038/s41698-023-00407-7.
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Front Pharmacol. 2023 Mar 27;14:1073037. doi: 10.3389/fphar.2023.1073037. eCollection 2023.