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The role of Pin1 in the development and treatment of cancer

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Abstract

Protein phosphorylation and post-phosphorylation events regulate many cellular signaling pathways. Peptidyl-prolyl isomerase (Pin1) is the only peptidyl-prolyl cis/trans isomerase that interacts with numerous oncogenic or tumor suppressive phosphorylated proteins, causes conformational changes in target proteins, and eventually regulates the activities of such proteins. These alterations in activity play a pivotal role in tumorigenesis. Since Pin1 is overexpressed and/or activated in various types of cancers, and the dysregulation of proline-directed phosphorylation contributes to tumorigenesis, Pin1 represents an attractive target for cancer therapy. This review will describe the role of Pin1 in cancer and the current status of Pin1 inhibitor development.

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Acknowledgments

Drs. Lu and Dr. Zhou are inventors of Pin1 technology, which was licensed by BIDMC to Pinteon Therapeutics. Both Dr. Lu and Dr. Zhou own equity in, and consult for, Pinteon and their interests were reviewed and are managed by BIDMC in accordance with its conflict of interest policy. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (2013-R1A1A1007596 and 2015M3A9C7030181). Work conducted in the authors’ laboratories is supported by National Institutes of Health (NIH) grants R01CA167677, R03DA031663, R01HL111430, R01AG029385 and R01AG046319, by the Alzheimer’s Association grant DVT-14-322623, and the National Natural Science Foundation of China (NSFC) grant U1205024 to K.P.L. Work is also supported by a Beth Israel Deaconess Medical Center pilot grant and generous gift donations from the Owens Family Foundation to X.Z.Z. and K.P.L.

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    1. New Drug Development Center, DGMIF, 80 Cheombok-ro Dong-gu, Daegu, 701-310, Korea

      Sang-Hyun Min

    2. Division of Translational Therapeutics, Department of Medicine and Cancer Research Institute, Center for Life Science, Beth Israel Deaconess Medical Center, Harvard Medical School, Room 0408, 330 Brookline Avenue, Boston, MA, 02215, USA

      Xiao Zhen Zhou & Kun Ping Lu

    3. Institute for Translational Medicine, Fujian Medical University, Fuzhou, 350108, China

      Kun Ping Lu

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    Sang-Hyun Min, Xiao Zhen Zhou, and Kun Ping Lu contributed equally to this work.

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    Min, SH., Zhou, X.Z. & Lu, K.P. The role of Pin1 in the development and treatment of cancer. Arch. Pharm. Res. 39, 1609–1620 (2016). https://doi.org/10.1007/s12272-016-0821-x

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