Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Gastroenterology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Eur J Pharmacol. 2019 Feb 15;845:8-15. doi: 10.1016/j.ejphar.2018.12.035. Epub 2018 Dec 22.
Increased aerobic glycolysis is considered as a hallmark of cancer and targeting key glycolytic enzymes will be a promising therapeutic approach in cancer treatment. Alpha-enolase (ENO1), as a prominent glycolytic enzyme, is upregulated in multiple cancers and its overexpression is involved in tumor cell proliferation and metastasis. In the present study, we aimed to investigate the potential role of ENO1 in the development and progression of gastric cancer (GC). Here, we found that ENO1 expression was upregulated in human GC and was associated with Lauren type, lymph node metastasis (LNM) and TNM stage. Knockdown of ENO1 attenuated GC cell proliferation and metastasis and reversed epithelial-mesenchymal transition (EMT) progress in vitro while ENO1 overexpression did the opposite. ENO1 could modulate AKT signaling pathway in GC cells and the enhanced proliferation and migration ability induced by ENO1 overexpression was impaired after incubation with PI3K inhibitor Ly294002 in SGC7901 cells. Our data demonstrated that ENO1 enhances GC cell proliferation and metastasis through the protein kinase B (AKT) signaling pathway, indicating that ENO1/AKT signaling axis may serve as a potential target for treatment of GC.
糖酵解增加被认为是癌症的一个标志，靶向关键的糖酵解酶将成为癌症治疗中一种有前途的治疗方法。α-烯醇化酶（ENO1）作为一种重要的糖酵解酶，在多种癌症中上调，其过表达参与肿瘤细胞的增殖和转移。在本研究中，我们旨在研究 ENO1 在胃癌（GC）发生和发展中的潜在作用。结果发现，ENO1 在人 GC 中表达上调，并与 Lauren 型、淋巴结转移（LNM）和 TNM 分期相关。ENO1 敲低可抑制 GC 细胞增殖和转移，并逆转体外上皮-间充质转化（EMT）进程，而 ENO1 过表达则相反。ENO1 可调节 GC 细胞中的 AKT 信号通路，在用 PI3K 抑制剂 Ly294002 孵育 SGC7901 细胞后，可削弱 ENO1 过表达诱导的增殖和迁移能力。本研究数据表明，ENO1 通过蛋白激酶 B（AKT）信号通路增强 GC 细胞的增殖和转移，表明 ENO1/AKT 信号轴可能成为治疗 GC 的潜在靶点。
