B cell CLL/lymphoma 6 member B inhibits hepatocellular carcinoma metastases in vitro and in mice
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AbstractB 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. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.
All Author(s) ListWang J, Dong L, Xu LX, Chu ESH, Chen YC, Shen JY, Li XX, Wong CC, Sung JJY, Yu J
Journal nameCancer Letters
Year2014
Month12
Day28
Volume Number355
Issue Number2
PublisherElsevier
Pages192 - 200
ISSN0304-3835
eISSN1872-7980
LanguagesEnglish-United Kingdom
KeywordsB cell CLL/Iymphoma 6 member B; Epigenetic alteration; Hepatocellular carcinoma; Tumor metastasis; Tumor suppressive gene
Web of Science Subject CategoriesOncology

Last updated on 2020-18-09 at 01:10