Department of Gynaecology, The Fourth Affiliated Hospital of Xinjiang Medical University, No. 116 Huanghe Road, Tianshan District, Urumqi City, 830000, Xinjiang Uygur Autonomous Region, China.
Hum Cell. 2020 Jul;33(3):790-800. doi: 10.1007/s13577-020-00356-4. Epub 2020 Apr 18.
Anterior gradient 2 (AGR2) was proved to modulate cancer progression. However, the role of AGR2 on endometrial cancer was not established. Here, we investigated the effects of AGR2 expression on endometrial cancer and explored the regulation mechanism. In the study, we found that AGR2 was overexpressed in tumor tissues of 30 endometrial cancer patients. A high level of AGR2 promoted endometrial cancer cells proliferation, migration and invasion. AGR2 induced the expression of lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), kallikrein 2 (HK2), and enolase 1-α (ENO1), glucose uptake and lactate production. AGR2 could bind to MUC1 and induce MUC1 and hypoxia-inducible factor 1α (HIF-1α). The inhibition effects of AGR2 knockdown on cells proliferation, migration and invasion ability were abolished by the overexpression of MUC1. Besides, the overexpression of MUC1 also reversed the inhibition effects of AGR2 knockdown on the expression of LDHA, HK2, PGK1 and ENO1, glucose uptake and lactate production. AGR2 knockdown inhibited tumor growth, the levels of Ki-67, MUC1, HIF-1α and glycolysis. In conclusion, AGR2 was overexpressed in endometrial cancer and AGR2-induced glucose metabolism facilitated the progression of endometrial carcinoma via the MUC1/HIF-1α pathway. AGR2 may be an effective therapeutic target for endometrial carcinoma.
前置梯度 2 (AGR2) 已被证明可调节癌症进展。然而，AGR2 对子宫内膜癌的作用尚未确定。在这里，我们研究了 AGR2 表达对子宫内膜癌的影响，并探讨了其调节机制。在这项研究中，我们发现 30 名子宫内膜癌患者的肿瘤组织中 AGR2 过表达。高水平的 AGR2 促进了子宫内膜癌细胞的增殖、迁移和侵袭。AGR2 诱导了乳酸脱氢酶 A (LDHA)、磷酸甘油酸激酶 1 (PGK1)、激肽释放酶 2 (HK2) 和烯醇酶 1-α (ENO1)、葡萄糖摄取和乳酸生成的表达。AGR2 可以与 MUC1 结合，并诱导 MUC1 和缺氧诱导因子 1α (HIF-1α) 的表达。AGR2 敲低对细胞增殖、迁移和侵袭能力的抑制作用被 MUC1 的过表达所消除。此外，MUC1 的过表达也逆转了 AGR2 敲低对 LDHA、HK2、PGK1 和 ENO1、葡萄糖摄取和乳酸生成表达的抑制作用。AGR2 敲低抑制肿瘤生长、Ki-67、MUC1、HIF-1α 和糖酵解的水平。总之，AGR2 在子宫内膜癌中过表达，AGR2 诱导的葡萄糖代谢通过 MUC1/HIF-1α 通路促进了子宫内膜癌的进展。AGR2 可能是子宫内膜癌的有效治疗靶点。
