title: B cell CLL/lymphoma 6 member B inhibits hepatocellular carcinoma metastases in vitro and in mice.
abstract: B cell CLL/lymphoma 6 member B (BCL6B) is a novel tumor suppressor silenced in human cancer. In this study, we investigated the functional role and underlying mechanisms of BCL6B in hepatocellular carcinoma (HCC). BCL6B was expressed in normal HCC tissues, but its expression was suppressed in 6 out of 9 HCC cell lines. Loss of BCL6B expression was associated with promoter hypermethylation. Ectopic expression of BCL6B in HepG2 and Huh7 cell lines inhibited colony formation (P <0.05), cell viability (P <0.01), and tumorigenicity in nude mice (P <0.05). BCL6B expression also induced apoptosis (P <0.05), an effect associated with activation of the caspase cascade and cleavage of PARP. Stable expression of BCL6B in MHCC97L cells suppressed cell migration (P <0.05) and invasion (P <0.05), and significantly reduced the incidence and severity of lung metastasis in an orthotopic HCC mouse model. The anti-metastatic effect of BCL6B was mediated by up-regulation of cell adhesion gene E-cadherin, OB-cadherin, HIV-1 Tat interactive protein 2, and transient receptor potential cation channel, subfamily M, member 1; and down-regulation of angiogenesis gene VEGFA. BCL6B functions as a tumor suppressor that inhibits HCC metastases in vitro and in vivo.
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Lixia
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Eagle S H
authors.initials: ES
authors.lastname: Chu
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong; School of Biomedical Science, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Yangchao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Chi Chun
authors.initials: CC
authors.lastname: Wong
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Shenzhen Research Insititute, The Chinese University of Hong Kong, Hong Kong. Electronic address: junyu@cuhk.edu.hk.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D020169:Caspases / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
chemical_list: C486398:BCL6B protein, human; D015820:Cadherins; D012097:Repressor Proteins; D014157:Transcription Factors; C086960:osteoblast cadherin; D020169:Caspases
keywords: B cell CLL/lymphoma 6 member B; Epigenetic alteration; Hepatocellular carcinoma; Tumor metastasis; Tumor suppressive gene