title: Methylation of DACT2 accelerates esophageal cancer development by activating Wnt signaling.
abstract: Esophageal cancer is one of the most common malignancies worldwide. DACT2 is frequently methylated in human lung, hepatic, gastric and thyroid cancers. The methylation status and function of DACT2 remain to be elucidated in human esophageal cancer. Ten esophageal cancer cell lines, 42 cases of dysplasia and 126 cases of primary esophageal cancer samples were analyzed in this study. The expression of DACT2 was detected in YES2 cells, while reduced DACT2 expression levels were found in TE8 and KYSE70 cells, and complete loss of DACT2 expression was found in KYSE30, KYSE140, KYSE150, KYSE410, KYSE450, TE3 and TE7 cells. Loss of expression or reduced expression of DACT2 correlated with promoter region hypermethylation in esophageal cancer cells. Restoration of DACT2 expression was induced by 5-aza-2'-deoxycytidine. In human primary esophageal squamous carcinoma, 69% (87/126) of samples were methylated. Methylation of DACT2 was significantly associated with tumor stage and metastasis (P < 0.01, P < 0.05). DACT2 suppressed colony formation, cell migration and invasion in esophageal cancer cells, and it also suppressed esophageal cancer cell xenograft growth. DACT2 inhibited Wnt signaling in human esophageal cancer cells. In conclusion, DACT2 is frequently methylated in human esophageal cancer and its expression is regulated by promoter region methylation. DACT2 suppresses esophageal cancer growth by inhibiting Wnt signaling.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.|Medical College of NanKai University, Tianjin 300071, China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Enqiang
authors.initials: E
authors.lastname: Linghu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R.China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Baoping
authors.initials: B
authors.lastname: Cao
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
authors.affiliation: The Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.affiliation: Medical College of NanKai University, Tianjin 300071, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C478653:DACT2 protein, human; D009363:Neoplasm Proteins
keywords: DACT2; Wnt signaling; esophageal cancer; metastasis; methylation