Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy

• Published in: Biomedicines Vol. 9; no. 4; p. 359
• Main Authors: Chuang, Hsiang-Hao, Zhen, Yen-Yi, Tsai, Yu-Chen, Chuang, Cheng-Hao, Huang, Ming-Shyan, Hsiao, Michael, Yang, Chih-Jen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.03.2021; MDPI
• Subjects: Antitumor activity; Binding sites; Breast cancer; Cancer; cancer therapeutics; Cancer therapies; Cell cycle; cell motility; Cell proliferation; cis-trans isomerization; Enzymes; Gene expression; Genomes; Kinases; Localization; Metastases; metastasis; MicroRNAs; Peptides; Peptidylprolyl isomerase; Phosphatase; Phosphorylation; Physiology; Pin1; Pin1 protein; Proline; Protein structure; Proteins; Review; Serine; Signal transduction; Threonine; Transcription factors; Tumorigenesis; cell motility; cancer therapeutics; Pin1; tumorigenesis; metastasis; cis-trans isomerization
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9040359

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.