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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.

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/fe69/11609185/9f13303fa299/fimmu-15-1482088-g001.jpg

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