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Abstract：
This review examines the complex role of Pin1 in the development and treatment of cancer. Pin1 is the only peptidyl-prolyl isomerase (PPIase) that can recognize and isomerize phosphorylated Ser/Thr-Pro peptide bonds. Pin1 catalyzes a structural change in phosphorylated Ser/Thr-Pro motifs that can modulate protein function and thereby impact cell cycle regulation and tumorigenesis. The molecular mechanisms by which Pin1 contributes to oncogenesis are reviewed, including Pin1 overexpression and its correlation with poor cancer prognosis, and the contribution of Pin1 to aggressive tumor phenotypes involved in therapeutic resistance is discussed, with an emphasis on cancer stem cells, the epithelial-to-mesenchymal transition (EMT), and immunosuppression. The therapeutic potential of Pin1 inhibition in cancer is discussed, along with the promise and the difficulties in identifying potent, drug-like, small-molecule Pin1 inhibitors. The available evidence supports the efficacy of targeting Pin1 as a novel cancer therapeutic by analyzing the role of Pin1 in a complex network of cancer-driving pathways and illustrating the potential of synergistic drug combinations with Pin1 inhibitors for treating aggressive and drug-resistant tumors.
摘要：
这篇综述探讨了Pin1在癌症发展和治疗中的复杂作用。Pin1是唯一可以识别和异构化磷酸化Ser/Thr-Pro肽键的肽基-氨酰异构酶（PPIase）。Pin1催化磷酸化Ser/Thr-Pro基序的结构变化，可以调节蛋白质功能，从而影响细胞周期调节和肿瘤发生。本文综述了Pin1促进肿瘤发生的分子机制。包括Pin1过表达及其与不良癌症预后的相关性，并讨论了Pin1对参与治疗抗性的侵袭性肿瘤表型的贡献，重点是癌症干细胞，上皮-间质转化（EMT），和免疫抑制。讨论了Pin1抑制在癌症中的治疗潜力，除了承诺和识别强权的困难，类似药物，小分子Pin1抑制剂。通过分析Pin1在癌症驱动途径的复杂网络中的作用，并说明与Pin1抑制剂的协同药物组合治疗侵袭性和耐药性肿瘤的潜力，现有证据支持靶向Pin1作为新型癌症治疗剂的功效。
