Research Papers:

LSD1 binds to HPV16 E7 and promotes the epithelial-mesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter

Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi and Sufang Wu _

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Oncotarget. 2017; 8:11329-11342. https://doi.org/10.18632/oncotarget.13516

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Yuan Liu1,*, Yanan Wang1,*, Chunqin Chen1,*, Jiawen Zhang1,2, Wenyan Qian3, Yu Dong4, Zhiqiang Liu5, Xi Zhang6, Xiaoyun Wang1, Zhenbo Zhang1, Xiaobing Shi7,8, Sufang Wu1

1Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China

2Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Shanghai Tongji University, Shanghai, China

3Department of Gynecology and Obstetrics, Kunshan Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Jiangsu, China

4Department of Obstetrics and Gynecology, Shanghai Xinhua hospital, Shanghai Jiaotong University, Shanghai, China

5Division of Cancer Medicine, Department of Lymphoma and Myeloma, Center for Cancer Immunology Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

6Department of Physiology and Neurobiology, University of Connecticut, CT, USA

7Department of Molecular Carcinogenesis and Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

8Genes and Development and Molecular Carcinogenesis Graduate Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA

*These authors have contributed equally to this work

Correspondence to:

Sufang Wu, email: [email protected]

Keywords: LSD1, HPV16E7, cervical cancer, EMT

Received: May 11, 2016    Accepted: October 17, 2016    Published: November 23, 2016


Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT). We proposed a novel mechanism, whereby LSD1 is recruited to the Vimentin promoter and demethylates H3K4me1 and H3K4me2. Notably, HPV16 E7 enhanced the expression of LSD1, formed a complex with LSD1, and suppressed LSD1 demethylase activity by hindering the recruitment of LSD1 to the Vimentin promoter. Thus, LSD1 is a primary and positive regulator of the HPV16 E7-induced EMT and an attractive therapeutic target for alleviating HPV16 E7-induced EMT and tumor metastasis.

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