Department of Gastrointestinal Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People's Republic of China.
The Affiliated Nanjing Drum Tower Clinical College of Nanjing Medical University, Nanjing 210002, People's Republic of China.
Mol Biol Cell. 2019 Sep 1;30(19):2527-2534. doi: 10.1091/mbc.E19-03-0136. Epub 2019 Jul 24.
The accumulation of adenosine in the tumor microenvironment is associated with tumor progression in many cancers. However, whether adenosine is involved in gastric cancer (GC) metastasis and progression, and the underlying molecular mechanism, is largely unclear. In this study, we find that GC tissues and cell lines had higher A2aR levels than nontumor gastric tissues and cell lines. A2aR expression correlated positively with TNMstage, and associated with poor outcomes. Adenosine enhanced the expression of the stemness and epithelial-mesenchymal transition-associated genes by binding to A2aR. A2aR expression on GC cells promoted metastasis in vivo. The PI3K-AKT-mTOR signaling pathway was involved in adenosine-stimulated GC cell migration and invasion. Our results indicate that adenosine promotes GC cell invasion and metastasis by interacting with A2aR to enhance PI3K-AKT-mTOR pathway signaling.
在许多癌症中，肿瘤微环境中腺苷的积累与肿瘤的进展有关。然而，腺苷是否参与胃癌（GC）的转移和进展，以及潜在的分子机制，在很大程度上还不清楚。在这项研究中，我们发现 GC 组织和细胞系比非肿瘤胃组织和细胞系具有更高的 A2aR 水平。A2aR 的表达与 TNM 分期呈正相关，并与不良预后相关。腺苷通过与 A2aR 结合增强了干性和上皮-间充质转化相关基因的表达。GC 细胞上的 A2aR 表达促进了体内转移。PI3K-AKT-mTOR 信号通路参与了腺苷刺激 GC 细胞迁移和侵袭。我们的结果表明，腺苷通过与 A2aR 相互作用增强 PI3K-AKT-mTOR 通路信号来促进 GC 细胞的侵袭和转移。
