Department of Biological Sciences, The University of Texas at Dallas, Richardson, Texas 75080, USA.
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
Nat Commun. 2017 May 26;8:15503. doi: 10.1038/ncomms15503.
Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.
腺癌 (ADC) 和鳞状细胞癌 (SqCC) 是非小细胞肺癌 (NSCLC) 的两种主要亚型，在组织学、分子和临床表现上有明显区别。然而，特定于 NSCLC 亚型的代谢特征仍不清楚。在这里，我们对人类 NSCLC 肿瘤样本、患者来源的异种移植物、NSCLC 小鼠模型、NSCLC 细胞系和癌症基因组图谱 (TCGA) 进行了综合分析，揭示了 GLUT1 葡萄糖转运蛋白在肺 SqCC 中的表达显著升高，这增加了葡萄糖摄取和糖酵解通量。我们表明，对糖酵解的严重依赖使肺 SqCC 容易受到糖酵解抑制，而肺 ADC 则表现出显著的葡萄糖独立性。临床上，肺 SqCC 中 GLUT1 介导的糖酵解升高与高 F-FDG 摄取和预后不良密切相关。这种 NSCLC 亚型以前未描述的代谢异质性表明，针对肺 SqCC 的诊断、预后和靶向治疗策略具有重要的潜在发展前景，而肺 SqCC 的现有治疗选择在临床上还不够充分。
