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REVIEW article

Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1343938
This article is part of the Research Topic

Phosphorylation-Dependent Peptidyl-Prolyl Cis/Trans Isomerase PIN1 - Volume II

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The Role of The Master Cancer Regulator Pin1 in The Development and Treatment of Cancer Provisionally Accepted

Robert Stewart1 Shaunik Sharma1 George Xie1 Timothy Wu1 Sho Okuda1 Xiao Zhen Zhou1* Brian Shilton1* Kun Ping Lu1*
  • 1Western University, Canada

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This review examines the complex role of Pin1 in the development and treatment of cancer. Pin1 is the only peptidyl-prolyl isomerase 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 is reviewed, including Pin1 overexpression and correlation with poor cancer prognosis, and the contribution of Pin1 to aggressive tumor phenotypes involved in therapeutic resistance with emphasis on cancer stem cells, the epithelial-mesenchymal transition, 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 analysing 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.

Keywords: Peptidyl-prolyl isomerase (PPIase), Pin1 inhibitors, Covalent inhibitors, cancer stem cells, Endothelial-mesenchyma transition [EnMT], Immunosuppression, oncogenesis, combination therapy

Received: 24 Nov 2023; Accepted: 28 Mar 2024.

Copyright: © 2024 Stewart, Sharma, Xie, Wu, Okuda, Zhou, Shilton and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Xiao Zhen Zhou, Western University, London, N6A 3K7, Ontario, Canada
Prof. Brian Shilton, Western University, London, N6A 3K7, Ontario, Canada
Prof. Kun Ping Lu, Western University, London, N6A 3K7, Ontario, Canada