C-terminal-truncated HBV X promotes hepato-oncogenesis through inhibition of tumor-suppressive β-catenin/BAMBI signaling
Experimental & Molecular Medicine
;
: e275-2016.
Article
in English
| WPRIM
| ID: wpr-149846
ABSTRACT
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein. Ectopic ctHBx expression generated more colonies in anchorage-dependent and -independent growth assays than did HBx expression alone. ctHBx downregulated BAMBI to a greater degree than did HBx in HCC cells. HBx activated the Wnt/β-catenin pathway, which positively regulated the BAMBI expression through T-cell factor 1 signaling, whereas ctHBx negatively regulated the Wnt/β-catenin pathway. BAMBI downregulated the β-catenin and TGF-β1 signaling pathways. TGF-β1 positively regulated BAMBI expression thorough Smad3 signaling. Furthermore, knockdown of BAMBI was more tumorigenic in HCC cells. Therefore, downregulation of both β-catenin and TGF-β1 signaling by BAMBI might contribute to tumor suppression in mice xenotransplanted with HepG2 or SH-J1 cells. Taken together, ctHBx may have a more oncogenic role than HBx through its inhibition of tumor-suppressive β-catenin/BAMBI signaling.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
T-Lymphocytes
/
Down-Regulation
/
Hepatitis B virus
/
Genome
/
Carcinoma, Hepatocellular
/
Bone Morphogenetic Proteins
/
Models, Animal
/
Activins
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2016
Type:
Article
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