Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy
2021
Hsiang-Hao Chuang | Yen-Yi Zhen | Yu-Chen Tsai | Cheng-Hao Chuang | Ming-Shyan Huang | Michael Hsiao | Chih-Jen Yang
Peptidyl-prolyl <i>cis-trans</i> 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.
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