title: Lysine-specific demethylase 1 promotes tumorigenesis and predicts prognosis in gallbladder cancer.
abstract: Gallbladder Cancer (GBC), characterized by invasive growth and infiltrative dissemination, is difficult to diagnose and has poor prognosis. Emerging evidence demonstrates that Lysine-Specific Demethylase 1 (LSD1) has important roles in carcinogenesis, proliferation and metastasis. We studied the roles and molecular mechanisms of LSD1 in GBC. We examined LSD1 expression in 109 paired samples of GBC and normal gallbladder tissues. We found GBC tissues had upregulated LSD1 compared with normal gallbladder tissues (P = 0.003), and its high expression was associated with tumor-node-metastasis stage (P < 0.0001), Nevin's stage (P = 0.0093) and distant metastases (P = 0.0070). We found positive correlations between LSD1 expression and other proteins: epithelial-mesenchymal transition markers, C-myc and cyclin-related proteins. Inhibiting LSD1 expression in vitro impaired the proliferation and invasiveness of GBC cells and also downregulated c-myc expression and consequently inhibited GBC cell proliferation. LSD1 overexpression promotes GBC development and may be a predictor for a worsened prognosis. LSD1 may be a novel therapeutic target and prognostic tool for gallbladder cancer.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Shi Xian
authors.initials: SX
authors.lastname: Lian
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Ye Bo
authors.initials: YB
authors.lastname: Shao
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Hou Bao
authors.initials: HB
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jun Yi
authors.initials: JY
authors.lastname: He
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Wei Qi
authors.initials: WQ
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D055785:Gene Knockdown Techniques; D064593:Heterografts; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011237:Predictive Value of Tests; D011379:Prognosis; D015854:Up-Regulation
chemical_list: D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: C-myc; gallbladder cancer; invasion and migration and proliferation; lysine-specific demethylase 1; prognosis