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Pin1:胰腺癌治疗潜力与抑制剂研究进展

Pin1: Advances in pancreatic cancer therapeutic potential and inhibitors research.

作者信息

Wang Nan, Chai Tian, Wang Xing-Rong, Zheng Yi-Dan, Sang Chun-Yan, Yang Jun-Li

机构信息

College of Pharmacy, Gansu University of Chinese Medicine; CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, China.

CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, China.

出版信息

Bioorg Chem. 2024 Dec;153:107869. doi: 10.1016/j.bioorg.2024.107869. Epub 2024 Oct 11.

Abstract

The peptidyl-prolyl cis/trans isomerase NIMA-interaction 1 (Pin1) catalyzes the transition of the proline ring from the cis to trans conformation, resulting in conformational and functional changes in proteins that are regulated by proline-guided serine/threonine phosphorylation. In recent years, Pin1 has emerged as a novel molecular target for the diagnosis and treatment of various malignant tumors. Notably, it has been found that Pin1 is highly expressed in pancreatic cancer. This article focuses on the mechanisms by which Pin1 orchestrates multiple oncogenic functions in the development of pancreatic cancer. By exploring the intricate interactions between Pin1 and the pancreatic tumor microenvironment, we provide an overview of Pin1's role in modifying glycolytic metabolism, redox balance, and the hypoxic microenvironment of pancreatic cancer. Furthermore, we summarize the potential anticancer effects of Pin1 inhibitors, aiming to elucidate Pin1's promise as a potential anticancer agent, particularly in the context of pancreatic cancer.

摘要

肽基脯氨酰顺反异构酶NIMA相互作用蛋白1(Pin1)催化脯氨酸环从顺式构象向反式构象的转变,导致受脯氨酸导向的丝氨酸/苏氨酸磷酸化调节的蛋白质发生构象和功能变化。近年来,Pin1已成为各种恶性肿瘤诊断和治疗的新型分子靶点。值得注意的是,已发现Pin1在胰腺癌中高表达。本文重点探讨Pin1在胰腺癌发生发展中协调多种致癌功能的机制。通过探索Pin1与胰腺肿瘤微环境之间的复杂相互作用,我们概述了Pin1在调节胰腺癌糖酵解代谢、氧化还原平衡和缺氧微环境中的作用。此外,我们总结了Pin1抑制剂的潜在抗癌作用,旨在阐明Pin1作为潜在抗癌药物的前景,特别是在胰腺癌背景下。

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