Theranostics 2020; 10(5):2188-2200. doi:10.7150/thno.39151 This issue

Research Paper

The SIRT2-mediated deacetylation of AKR1C1 is required for suppressing its pro-metastasis function in Non-Small Cell Lung Cancer

Hong Zhu1,#, Yan Hu1,#, Chenming Zeng1,#, Linlin Chang1, Fujin Ge1, Weihua Wang1, Fangjie Yan1, Qinxin Zhao1, Ji Cao1, Meidan Ying1, Yongchuan Gu2, Lin Zheng1, Qiaojun He1,✉, Bo Yang1,✉

1. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
2. Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand
#: These authors contribute equally to this study.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Zhu H, Hu Y, Zeng C, Chang L, Ge F, Wang W, Yan F, Zhao Q, Cao J, Ying M, Gu Y, Zheng L, He Q, Yang B. The SIRT2-mediated deacetylation of AKR1C1 is required for suppressing its pro-metastasis function in Non-Small Cell Lung Cancer. Theranostics 2020; 10(5):2188-2200. doi:10.7150/thno.39151. Available from

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Graphic abstract

Aldo-keto reductase family 1 member C1 (AKR1C1) promotes malignancy of Non-Small Cell Lung Cancer (NSCLC) by activating Signal Transducer and Activator of Transcription 3 (STAT3) pathway. However, how the pro-metastatic functions of AKR1C1 are switched on/off remains unknown.

Methods: Immunoprecipitation and LC-MS/MS analyses were performed to identify the acetylation on AKR1C1 protein, and the functional analyses (in vitro and in vivo) were performed to depict the contribution of acetylation to the pro-metastatic effects of AKR1C1.

Results: Here we report that acetylated AKR1C1 on two lysine residues K185 & K201 is critical to its pro-metastatic role. The acetylation modification has no impact on the canonical enzymatic activity of AKR1C1, while it is required for the interaction between AKR1C1 to STAT3, which triggers the downstream transduction events, ultimately mobilizing cells. Importantly, the deacetylase Sirtuin 2 (SIRT2) is capable of deacetylating AKR1C1, inhibiting the transactivation of STAT3 target genes, thus suppressing the migration of cells.

Conclusion: Acetylation on Lysines 185 and 201 of AKR1C1 dictates its pro-metastatic potential both in vitro and in vivo, and the reverting of acetylation by Sirtuin 2 provides potential therapeutic targets for treatment against metastatic NSCLC patients with high AKR1C1 expression.

Keywords: acetylation, AKR1C1, SIRT2, non-small cell lung cancer, metastasis