title: LSD1 binds to HPV16 E7 and promotes the epithelial-mesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chunqin
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.|Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Shanghai Tongji University, Shanghai, China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, Kunshan Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Jiangsu, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Xinhua hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Division 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.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, CT, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular Carcinogenesis and Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Genes and Development and Molecular Carcinogenesis Graduate Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000821:virology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D056466:Histone Demethylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology; D014746:Vimentin / Q000235:genetics*
chemical_list: D006657:Histones; D050725:Papillomavirus E7 Proteins; D014746:Vimentin; C059731:oncogene protein E7, Human papillomavirus type 16; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: EMT; HPV16E7; LSD1; cervical cancer