Tirinato Luca, Pagliari Francesca, Di Franco Simone, Sogne Elisa, Marafioti Maria Grazia, Jansen Jeanette, Falqui Andrea, Todaro Matilde, Candeloro Patrizio, Liberale Carlo, Seco Joao, Stassi Giorgio, Di Fabrizio Enzo
Biomedical Physics in Radiation Oncology, DKFZ (German Cancer Research Center), 69120 Heidelberg, Germany.
Physical Science and Engineering (PSE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Genes Dis. 2019 Sep 25;7(4):620-635. doi: 10.1016/j.gendis.2019.09.010. eCollection 2020 Dec.
Lipid Droplets (LDs) are emerging as crucial players in colon cancer development and maintenance. Their expression has been associated with high tumorigenicity in Cancer Stem Cells (CSCs), so that they have been proposed as a new functional marker in Colorectal Cancer Stem Cells (CR-CSCs). They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory molecules. There is growing evidence that a possible connection between metabolic alterations and malignant transformation exists, although the effects of nutrients, primarily glucose, on the CSC behavior are still mostly unexplored. Glucose is an essential fuel for cancer cells, and the connections with LDs in the healthy and CSC populations merit to be more deeply investigated. Here, we showed that a high glucose concentration activated the PI3K/AKT pathway and increased the expression of CD133 and CD44v6 CSC markers. Additionally, glucose was responsible for the increased amount of Reactive Oxygen Species (ROS) and LDs in both healthy and CR-CSC samples. We also investigated the gene modulations following the HG treatment and found out that the healthy cell gene profile was the most affected. Lastly, Atorvastatin, a lipid-lowering drug, induced the highest mortality on CR-CSCs without affecting the healthy counterpart.
脂滴（LDs）正逐渐成为结肠癌发生和维持过程中的关键因素。它们的表达与癌症干细胞（CSCs）的高致瘤性相关，因此被提议作为结直肠癌干细胞（CR-CSCs）的一种新的功能标志物。它们还通过促炎分子的产生间接参与肿瘤微环境的调节。越来越多的证据表明代谢改变与恶性转化之间可能存在联系，尽管营养物质（主要是葡萄糖）对CSC行为的影响仍大多未被探索。葡萄糖是癌细胞的重要燃料，其在健康细胞群体和CSC群体中与脂滴的联系值得更深入研究。在这里，我们表明高葡萄糖浓度激活了PI3K/AKT通路，并增加了CD133和CD44v6 CSC标志物的表达。此外，葡萄糖导致健康细胞和CR-CSC样本中活性氧（ROS）和脂滴数量增加。我们还研究了高糖处理后的基因调控情况，发现健康细胞的基因谱受影响最大。最后，降脂药物阿托伐他汀对CR-CSCs诱导的死亡率最高，而不影响健康细胞。
