B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma.
B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma.
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DOI：
10.3389/fmolb.2021.656151
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发表时间：
2021
影响因子：
5
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Liu T;Yu J;Ge C;Zhao F;Miao C;Jin W;Su Y;Geng Q;Chen T;Xie H;Cui Y;Yao M;Li J;Hou H;Li H
肝细胞癌（Hepatocellular carcinoma，HCC）是世界范围内致死率最高的恶性肿瘤之一，具有高度异质性和易转移的特点。新的证据表明，BAP 31参与了不同类型的癌症进展。BAP 31是否以及如何在HCC转移中发挥作用仍是未知数。上皮间质转化（Epithelial-mesenchymal transition，EMT）是肿瘤微环境中常见的特征，其诱导剂TGF-β可增加BAP 31的表达。BAP 31的高表达与肝癌的大小、血管浸润和预后不良呈正相关。BAP 31的异位表达促进了细胞的迁移和侵袭，而BAP 31的敲低显著减弱了HCC细胞和小鼠原位异种移植物的转移潜能。BAP 31可诱导EMT过程，增强EMT相关因子Snail的表达，降低E-cadherin的含量和膜分布。BAP 31还激活AKT/β-catenin通路，从而介导其促进HCC转移的作用。AKT抑制剂进一步抵消了BAP 31过表达时激活的AKT/β-catenin/Snail。此外，在BAP 31过表达的细胞中沉默Snail会损害HCC细胞增强的迁移和侵袭能力。在肝癌组织中，BAP 31的表达与Snail呈正相关。结论BAP 31通过激活AKT/β-catenin/Snail通路促进肝癌转移。因此，我们的研究暗示BAP 31作为潜在的预后生物标志物，并为HCC的预后和治疗提供有价值的信息。
Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide, characterized with high heterogeneity and inclination to metastasize. Emerging evidence suggests that BAP31 gets involved in cancer progression with different kinds. It still remains unknown whether and how BAP31 plays a role in HCC metastasis. Epithelial–mesenchymal transition (EMT) has been a common feature in tumor micro-environment, whose inducer TGF-β increased BAP31 expression in this research. Elevated expression of BAP31 was positively correlated with tumor size, vascular invasion and poor prognosis in human HCC. Ectopic expression of BAP31 promoted cell migration and invasion while BAP31 knockdown markedly attenuated metastatic potential in HCC cells and mice orthotopic xenografts. BAP31 induced EMT process, and enhanced the expression level of EMT-related factor Snail and decreased contents and membrane distribution of E-cadherin. BAP31 also activated AKT/β-catenin pathway, which mediated its promotional effects on HCC metastasis. AKT inhibitor further counteracted the activated AKT/β-catenin/Snail upon BAP31 over-expression. Moreover, silencing Snail in BAP31-overexpressed cells impaired enhanced migratory and invasive abilities of HCC cells. In HCC tissues, BAP31 expression was positively associated with Snail. In conclusion, BAP31 promotes HCC metastasis by activating AKT/β-catenin/Snail pathway. Thus, our study implicates BAP31 as potential prognostic biomarker, and provides valuable information for HCC prognosis and treatment.