ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal squamous cell carcinoma

// So-Young Yeo 1,* , Sang Yun Ha 2,* , Eun Ji Yu 1 , Keun-Woo Lee 1 , Jeong Hoon Kim 1,3 and Seok-Hyung Kim 1,2 1 Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea 2 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea * These authors contributed equally to this work Correspondence: Jeong Hoon Kim, email: // Seok-Hyung Kim, email: // Keywords : ZNF282, E2F1, Cell cycle, Esophageal squamous cell carcinoma, Prognosis Received : May 14, 2014 Accepted : October 23, 2014 Published : October 24, 2014 Abstract Zinc finger protein 282 (ZNF282) is a newly identified transcription factor and little is known about its expression and function. Originally, ZNF282 is known to bind U5RE (U5 repressive element) of HLTV-1 (human T cell leukemia virus type 1) with a repressive effect. Recently we reported that ZNF282 functions as an estrogen receptor co-activator and plays an essential role in breast tumorigenesis. Although these results suggest the possible role of ZNF282 in cancers, clinical significance and function of ZNF282 are completely unknown in most of cancers. Here we found that ZNF282 was frequently overexpressed in esophageal squamous cell carcinoma (ESCC) (n=165) compared with normal esophageal epithelium and its overexpression was correlated with adverse clinical outcome. Multivariate survival analysis indicated that ZNF282 expression was an independent prognostic predictor for poor survival in ESCC (HR: 2.56 (95% CI 1.54-4.26), p <0.001). In addition, depletion of ZNF282 inhibited the cell cycle progression, migration, and invasion of ESCC cells and reduced the tumorigenicity of ESCC xenograft in nude mouse. We further showed that ZNF282 is required for E2F1-mediated gene expression in ESCC cells. Thus, ZNF282 is E2F1 co-activator involved in ESCC and elevated expression of ZNF282 is an independent adverse prognostic factor in ESCC.