Wu Mengjie, Ding Yongfeng, Jiang Xiaoxia, Chen Yanyan, Wu Nan, Li Linrong, Wang Haiyong, Huang Yingying, Xu Nong, Teng Lisong
Cancer Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2020 Jan 17;9:1544. doi: 10.3389/fonc.2019.01544. eCollection 2019.
Gastric cancer (GC) is a frequently occurring malignancy with high mortality rates. However, the underlying mechanism of GC progression is not very clear. The aim of this study is to reveal the inherent molecular mechanism and develop potential therapeutic targets for advanced GC. The microfibril-associated glycoprotein 1 (MAGP1), identified as a potential oncogene, was found upregulated in GC tissues and high MAGP1 expression was associated with aggressive clinicopathological features. Furthermore, the multivariate Cox regression analysis showed that high MAGP1 expression was an independent predictor of poor prognosis (HR = 2.37, 1.07-5.24; = 0.033). Mechanistically, MAGP1 promoted the migration and invasiveness of GC cells. In addition, the genes co-expressed with MAGP1 were primarily enriched in focal adhesion and PI3K-Akt pathways. MAGP1 overexpression enhanced the phosphorylation of FAK, AKT, and mTOR, whereas its knockdown also inactivated these factors. Furthermore, the AKT inhibitor suppressed the phosphorylation of AKT, FAK, and mTOR in recMAGP1-treated AGS cells, as well as their migration and invasion capacities. Finally, correlation analysis indicated that MAGP1 is involved in AKT signaling in GC, and is clinically relevant. Taken together, MAGP1 is a promising prognostic marker and potential therapeutic target for advanced GC.
胃癌（GC）是一种常见的恶性肿瘤，死亡率很高。然而，GC进展的潜在机制尚不完全清楚。本研究的目的是揭示其内在分子机制，并为晚期GC开发潜在的治疗靶点。微原纤维相关糖蛋白1（MAGP1）被确定为一种潜在的癌基因，在GC组织中上调，且高MAGP1表达与侵袭性临床病理特征相关。此外，多因素Cox回归分析表明，高MAGP1表达是预后不良的独立预测因素（HR = 2.37，1.07 - 5.24；P = 0.033）。机制上，MAGP1促进GC细胞的迁移和侵袭。此外，与MAGP1共表达的基因主要富集于粘着斑和PI3K - Akt信号通路。MAGP1过表达增强了FAK、AKT和mTOR的磷酸化，而其敲低也使这些因子失活。此外，AKT抑制剂抑制了recMAGP1处理的AGS细胞中AKT、FAK和mTOR的磷酸化，以及它们的迁移和侵袭能力。最后，相关性分析表明，MAGP1参与GC中的AKT信号传导，且具有临床相关性。综上所述，MAGP1是晚期GC有前景的预后标志物和潜在治疗靶点。
