Research Papers:

HDAC10 promotes lung cancer proliferation via AKT phosphorylation

Yiwei Yang _, Yitong Huang, Zhantong Wang, Hsin-tzu Wang, Baoyu Duan, Dan Ye, Chenxin Wang, Ruiqi Jing, Ye Leng, Jiajie Xi, Wen Chen, Guiying Wang, Wenwen Jia, Songcheng Zhu and Jiuhong Kang

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Oncotarget. 2016; 7:59388-59401. https://doi.org/10.18632/oncotarget.10673

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Yiwei Yang1,*, Yitong Huang1,*, Zhantong Wang1, Hsin-tzu Wang1, Baoyu Duan1, Dan Ye1, Chenxin Wang1, Ruiqi Jing1, Ye Leng1, Jiajie Xi1, Wen Chen1, Guiying Wang1, Wenwen Jia1, Songcheng Zhu1, Jiuhong Kang1

1Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai 200092, P. R. China

*These authors have contributed equally to this work

Correspondence to:

Songcheng Zhu, email: [email protected]

Jiuhong Kang, email: [email protected]

Keywords: lung cancer, histone deacetylase 10 (HDAC10), AKT, cell cycle, cellular localization

Received: November 19, 2015    Accepted: July 06, 2016    Published: July 18, 2016


Histone deacetylase 10 (HDAC10) is a member of the class II HDACs, and its role in cancer is emerging. In this study, we found that HDAC10 is highly expressed in lung cancer tissues. It resides mainly in the cytoplasm of lung cancer cells but resides in the nucleus of adjacent normal cells. Further examinations revealed that HDAC10 resides in the cytoplasm in multiple lung cancer cell lines, including the A549, H358 and H460 cell lines, but mainly resides in the nucleus of normal lung epithelial 16HBE cells. A leucine-rich motif, R505L506L507C508V509A510L511, was identified as its nuclear localization signal (NLS), and a mutant (Mut-505-511) featuring mutations to A at each of its original R and L positions was found to be nuclear-localization defective. Functional analysis revealed that HDAC10 promoted lung cancer cell growth and that its knockdown induced cell cycle arrest and apoptosis. Mechanistic studies showed that HDAC10 knockdown significantly decreased the phosphorylation of AKT at Ser473 and that AKT expression significantly rescued the cell cycle arrest and apoptosis elicited by HDAC10 knockdown. A co-immunoprecipitation assay suggested that HDAC10 interacts with AKT and that inhibition of HDAC10 activity decreases its interaction with and phosphorylation of AKT. Finally, we confirmed that HDAC10 promoted lung cancer proliferation in a mouse model. Our study demonstrated that HDAC10 localizes and functions in the cytoplasm of lung cancer cells, thereby underscoring its potential role in the diagnosis and treatment of lung cancer.

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