title: Elf3 drives β-catenin transactivation and associates with poor prognosis in colorectal cancer.
abstract: Aberrant regulation of the Wnt/β-catenin pathway plays important roles in colorectal carcinogenesis, with over 90% of cases of sporadic colon cancer featuring β-catenin accumulation. While ubiquitination-mediated degradation is widely accepted as a major route for β-catenin protein turnover, little is known about the regulation of β-catenin in transcriptional level. Here we show that Elf3, a member of the E-twenty-six family of transcription factors, drives β-catenin transactivation and associates with poor survival of colorectal cancer (CRC) patients. We first found recurrent amplification and upregulation of Elf3 in CRC tissues, and further Gene Set Enrichment Analysis identified significant association between Elf3 expression and activity of WNT/β-catenin pathway. Chromatin immunoprecipitation and electrophoretic mobility shift assay consistently revealed that Elf3 binds to and transactivates β-catenin promoter. Ectopic expression of Elf3 induces accumulation of β-catenin in both nucleus and cytoplasm, causing subsequent upregulation of several effector genes including c-Myc, VEGF, CCND1, MMP-7 and c-Jun. Suppressing Elf3 in CRC cells attenuates β-catenin signaling and decreases cell proliferation, migration and survival. Targeting Elf3 in xenograft tumors suppressed tumor progression in vivo. Taken together, our data identify Elf3 as a pivotal driver for β-catenin signaling in CRC, and highlight potential prognostic and therapeutic significance of Elf3 in CRC.
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: J-L
authors.initials: JL
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: Z-F
authors.initials: ZF
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: H-M
authors.initials: HM
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: M-Y
authors.initials: MY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: T-T
authors.initials: TT
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Department of Gastroenterology and Hepatology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Fang
mesh_terms: D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D009363:Neoplasm Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D051176:beta Catenin