Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, China.
J Cell Biochem. 2018 Dec;119(12):10013-10020. doi: 10.1002/jcb.27331. Epub 2018 Aug 26.
Hypoxia induces epithelial-mesenchymal transition (EMT) in tumorigenesis. A-kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia-inducible factor-1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia-induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/β-catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia-induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/β-catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer.
缺氧诱导肿瘤发生中的上皮-间充质转化（EMT）。A-激酶锚蛋白 4（AKAP4）是 AKAPs 家族的一员，在肿瘤发生中发挥关键作用。然而，AKAP4 在胃癌中的生物学作用尚不清楚。因此，我们研究了 AKAP4 在缺氧条件下对人胃癌细胞 EMT 的影响。结果表明，AKAP4 在人胃癌细胞系中表达显著上调。此外，缺氧诱导因子-1α 的沉默表达显著抑制了缺氧条件下胃癌细胞中 AKAP4 的表达。此外，AKAP4 的敲低显著阻止了缺氧诱导的胃癌细胞迁移、侵袭和 EMT 过程。在机制上，AKAP4 的敲低阻止了缺氧条件下胃癌细胞中 Wnt/β-catenin 通路的激活。这些发现表明，AKAP4 的敲低通过抑制 Wnt/β-catenin 信号通路抑制人胃癌细胞缺氧诱导的 EMT。因此，AKAP4 可能是治疗胃癌的潜在治疗靶点。
