Targeting TRIM54/Axin1/β-Catenin Axis Prohibits Proliferation and Metastasis in Hepatocellular Carcinoma

Accumulating evidence demonstrates that dysregulation of ubiquitin-mediated degradation of oncogene or suppressors plays an important role in several diseases. However, the function and molecular mechanisms of ubiquitin ligases underlying hepatocellular carcinoma (HCC) remain elusive. In the current...

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Bibliographic Details
Published in:Frontiers in oncology 2021-12, Vol.11, p.759842-759842
Main Authors: Zhu, Jinrong, Wu, Yongqi, Lao, Shaoxi, Shen, Jianfei, Yu, Yijian, Fang, Chunqiang, Zhang, Na, Li, Yan, Zhang, Rongxin
Format: Article
Language:English
Subjects:
hepatocellular carcinoma
metastasis
Oncology
proliferation
TRIM54
ubiquitination
Wnt/β-catenin signaling
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Summary:Accumulating evidence demonstrates that dysregulation of ubiquitin-mediated degradation of oncogene or suppressors plays an important role in several diseases. However, the function and molecular mechanisms of ubiquitin ligases underlying hepatocellular carcinoma (HCC) remain elusive. In the current study, we show that overexpression of TRIM54 was associated with HCC progression. TRIM54 overexpression facilitates proliferation and lung metastasis; however, inhibition of TRIM54 significantly suppressed HCC progression both and . Mechanically, we demonstrated that TRIM54 directly interacts with Axis inhibition proteins 1 (Axin1) and induces E3 ligase-dependent proteasomal turnover of Axin1 and substantially induces sustained activation of wnt/β-catenin in HCC cell lines. Furthermore, we showed that inhibition of the wnt/β-catenin signaling pathway small molecule inhibitors significantly suppressed TRIM54-induced proliferation. Our data suggest that TRIM54 might function as an oncogenic gene and targeting the TRIM54/Axin1/β-catenin axis signaling may be a promising prognostic factor and a valuable therapeutic target for HCC.
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2021.759842