International Journal of Medical Sciences

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25 May 2019

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Int J Med Sci 2018; 15(13):1573-1581. doi:10.7150/ijms.27426

Research Paper

Pin1 Is Involved in HDAC6-mediated Cancer Cell Motility

Hsiang-Hao Chuang1*, Ming-Shyan Huang2,3*, Pei-Hui Wang1, Yu-Peng Liu4, Michael Hsiao5, Chih-Jen Yang1,6,7✉

1. Division of Pulmonary and Critical Care Medicine and Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2. Department of Internal Medicine, E-DA Cancer Hospital, Kaohsiung, Taiwan
3. School of Medicine, I-Shou University, Kaohsiung, Taiwan
4. Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5. Genomics Research Center, Academia Sinica, Taipei, Taiwan
6. Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
7. Faculty of Medicine, Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Taiwan
*These authors contributed equally to this work.


Histone deacetylase 6 (HDAC6), a member of the HDAC enzymes, has been reported to play substantial roles in many cellular processes. Evidence shows that deregulation of HDAC6 may be involved in the progression of some cancers, neurodegenerative diseases, and inflammatory disorders. However, little is known regarding the effect of post-translational modification of HDAC6 on cellular localization and biological functions. In the present study, we identified four phosphorylation sites on HDAC6 under normal conditions by mass spectrometry analysis. Two phosphorylation sites, pSer22 and pSer412, are recognized as Pin1 (peptidyl-prolyl cis/trans isomerase NIMA-interacting 1) substrates. Pin1 can interact with HDAC6 and be involved in HDAC6-mediated cell motility. Pin1 depletion abrogates HDAC6-induced cell migration and invasion in H1299 lung cancer cells. The findings of this study suggest that Pin1 might regulate HDAC6-mediated cell motility through alteration of protein conformation and function. Our results indicate the complexity of activity regulation between HDAC6 and Pin1, expanding knowledge regarding the multifunctional roles of Pin1 in tumorigenesis and cancer progression.

Keywords: HDAC6, invasion, migration, Pin1.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Chuang HH, Huang MS, Wang PH, Liu YP, Hsiao M, Yang CJ. Pin1 Is Involved in HDAC6-mediated Cancer Cell Motility. Int J Med Sci 2018; 15(13):1573-1581. doi:10.7150/ijms.27426. Available from