Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis.
Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis.
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AJAP1/β-连环蛋白/ZEB1信号失调促进肝细胞癌的癌变和转移
DOI：
10.1038/cddis.2017.126
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发表时间：
2017-04-06
影响因子：
9
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Han J;Xie C;Pei T;Wang J;Lan Y;Huang K;Cui Y;Wang F;Zhang J;Pan S;Liang Y;Zhen T;Song R;Sun B;Li Y;Shi H;Yang G;Liu X;Zhu M;Wang Y;Li K;Liu Y;Meng F;Liao F;Meng X;Hong X;Liu L
粘附连接相关蛋白1 （AJAP1）是一种完整的膜蛋白，被认为在各种恶性肿瘤中起肿瘤抑制作用。下调AJAP1 mRNA水平可能预测肝细胞癌（HCC）患者的复发，但其潜在的分子机制尚不清楚。本研究通过检测AJAP1在体外、人类标本和小鼠异种移植模型中肝癌细胞增殖、迁移和侵袭中的作用来解决这一问题。我们发现AJAP1在HCC细胞和人HCC组织中表达降低，并与转移有关。AJAP1过表达抑制HCC的进展和转移，而其沉默在体外和体内均具有相反的作用。此外，AJAP1通过与β-catenin相互作用，抑制其核易位，从而抑制锌指E-box binding homeobox 1 （ZEB1）的转录，从而阻断上皮细胞向间质细胞的转化。这些结果表明，AJAP1抑制HCC转移，因此是HCC治疗的潜在治疗靶点。
Adherens junctions-associated protein 1 (AJAP1) is an integral membrane protein that is thought to function as a tumor suppressor in various malignancies. Downregulation of AJAP1 mRNA levels may predict recurrence in hepatocellular carcinoma (HCC) patients, but the underlying molecular mechanism is unknown. This was addressed in the present study by examining the role of AJAP1 in HCC cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. We found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis. AJAP1 overexpression inhibited HCC progression and metastasis, while its silencing had the opposite effect both in vitro and in vivo. Furthermore, AJAP1 blocked epithelial–to–mesenchymal transition by interacting with β-catenin and inhibiting its nuclear translocation, which suppressed zinc finger E-box binding homeobox 1 (ZEB1) transcription. These results indicate that AJAP1 inhibits HCC metastasis, and is thus a potential therapeutic target for HCC treatment.