The aerobic glycolytic pathway, boosting lactate formation, and glutamine addiction are two hallmarks of cancer pathophysiology. Consistent with this, several cell membrane glutamine transporters, belonging to different solute carrier (SLC) families, have been shown to be upregulated in a cell-specific manner to furnish the cells with glutamine and glutamine-derived metabolic intermediates. Among them, the system A transporter Slc38a1 has a higher affinity for glutamine compared to other SLC transporters, and it undergoes highly multifaceted regulation at gene and protein levels. The current study aimed to investigate the functional role of Slc38a1 in the proliferation and maturation of the mouse tongue epithelium. Secondly, we aimed to examine the expression ofSLC38A1and its regulation in human tongue oral squamous cell carcinoma (OTSCC). EmployingSlc38a1wild-type and knockout mice, we showed that Slc38a1 was not directly linked to the regulation of the proliferation and differentiation of the mouse tongue epithelium. External transcriptomic datasets and Western blot analyses showed upregulation ofSLC38A1mRNA/protein in human OTSCC and oral cancer cell lines as compared to the corresponding controls. Further, an investigation of external datasets indicated that mechanisms other than the amplification of theSLC38A1chromosomal locus or hypomethylation of theSLC38A1promoter region might be important for the upregulation ofSLC38A1in OTSCC.
有氧糖酵解途径促进乳酸生成，以及谷氨酰胺依赖是癌症病理生理学的两个标志性特征。与此一致，多种属于不同溶质载体（SLC）家族的细胞膜谷氨酰胺转运蛋白已被证明以细胞特异性方式上调，为细胞提供谷氨酰胺及谷氨酰胺衍生的代谢中间产物。其中，系统A转运蛋白Slc38a1相较于其他SLC转运蛋白对谷氨酰胺具有更高亲和力，并在基因和蛋白质水平受到高度多层次的调控。本研究旨在探讨Slc38a1在小鼠舌上皮细胞增殖和成熟中的功能作用。其次，我们旨在检测SLC38A1在人口腔舌鳞状细胞癌（OTSCC）中的表达及其调控机制。通过使用Slc38a1野生型和基因敲除小鼠，我们发现Slc38a1与小鼠舌上皮细胞增殖和分化的调控无直接关联。外部转录组数据集和蛋白质印迹分析显示，与相应对照组相比，人类OTSCC及口腔癌细胞系中SLC38A1 mRNA/蛋白表达上调。此外，对外部数据集的进一步研究表明，在OTSCC中SLC38A1的上调可能主要依赖于SLC38A1染色体位点扩增或启动子区域低甲基化以外的其他机制。
肿瘤(癌症)患者之家