期刊
ONCOTARGET
卷 7, 期 37, 页码 59388-59401出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10673
关键词
lung cancer; histone deacetylase 10 (HDAC10); AKT; cell cycle; cellular localization
资金
- Ministry of Science and Technology [2013CB967401, 2013CB967600]
- National Natural Science Foundation of China [31571390, 81530042, 91519320, 31210103905, 31571519, 31571529, 31401257, 31371510, 31471250, 31401126]
- Ministry of Education [IRT_15R51]
- Science and Technology Commission of Shanghai Municipality [15JC1403200]
- Shanghai Rising-Star Program [14QA1403900]
- Fundamental Research Funds for the Central Universities [20002310002, 2000219136, 1507219042, 1500219106]
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, R(505)L(506)L(507)C(508)V(509)A(510)L(511), 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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