Wang Yanfen, Shi Shanshan, Ding Yongling, Wang Zheng, Liu Shuang, Yang Jiajia, Xu Tongpeng
Department of Pathology, The Affliated Hospital of Yangzhou University, Yangzhou University Yangzhou, Jiangsu, P. R. China.
Department of Pathology, Jinling Hospital, Clinical Medical School of Southern Medical University Nanjing, Jiangsu, P. R. China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):10759-10769. eCollection 2017.
Lung adenocarcinoma (LAC) is one of the common reasons of cancer-related death with few biomarkers for diagnosis and prognosis. Solute carrier family 2 member 1 protein, SLC2A1, has been associated with tumor progression, metastasis, and poor prognosis in many human solid tumors. However, little is reported about its biological functions in lung adenocarcinoma. Here we observed a strong up-regulation of SLC2A1 in patients with LAC and found that SLC2A1 was significantly correlated with prognosis. Knockdown of SLC2A1 in LAC cells inhibits cellular proliferation and plate clone formation as well as suppression of glucose utilization. Meanwhile, silencing of SLC2A1 also suppresses tumor metastasis . Mechanistically, GSEA showed that genes in cell cycle pathway were prominently enriched in the higher SLC2A1 group. By a large-scale proteomic analysis, we revealed that cell cycle protein level was significantly increased in SLC2A1-high group. Collectively, our findings indicate that elevated SLC2A1 is a critical modulator in lung adenocarcinoma progression by altering glucose metabolism and the cell cycle pathway, and also suggest SLC2A1 as a promising target for lung adenocarcinoma therapy.
肺腺癌（LAC）是癌症相关死亡的常见原因之一，用于诊断和预后的生物标志物很少。溶质载体家族2成员1蛋白（SLC2A1）在许多人类实体瘤中与肿瘤进展、转移及不良预后相关。然而，关于其在肺腺癌中的生物学功能报道较少。在此，我们观察到肺腺癌患者中SLC2A1强烈上调，并发现SLC2A1与预后显著相关。敲低肺腺癌细胞中的SLC2A1可抑制细胞增殖和平板克隆形成以及抑制葡萄糖利用。同时，沉默SLC2A1也可抑制肿瘤转移。机制上，基因集富集分析（GSEA）显示细胞周期途径中的基因在SLC2A1水平较高的组中显著富集。通过大规模蛋白质组学分析，我们发现SLC2A1高表达组中细胞周期蛋白水平显著升高。总体而言，我们的研究结果表明，SLC2A1升高是肺腺癌进展中的关键调节因子，可通过改变葡萄糖代谢和细胞周期途径来实现，这也表明SLC2A1是肺腺癌治疗的一个有前景的靶点。
