ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells
Di Franco, Simone
Marafioti, Maria Grazia
Di Fabrizio, Enzo M.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Label-Free Optical Microscopy for Biology Lab
Material Science and Engineering Program
Physical Science and Engineering (PSE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/660317
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AbstractLipid 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.
CitationTirinato, L., Pagliari, F., Di Franco, S., Sogne, E., Marafioti, M. G., Jansen, J., … Di Fabrizio, E. (2019). ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells. Genes & Diseases. doi:10.1016/j.gendis.2019.09.010
SponsorsThis study was supported by Italian Association for Cancer Research (AIRC) and from the European Union's Horizon 2020 Research And Innovation Programme under the Marie Skłodowska-Curie grant agreement No 800924. This work was also supported by AIRC (5x1000 Clinical Oncology Extension Program 9979 and IG 16746). The authors acknowledge financial support from King Abdullah University of Science and Technology for OCRF-2014-CRG and OCRF-2016-CRG grants and from Piedmont Region through European Funds for Regional Development (“Food Digital Monitoring” project). This work is dedicated to the memory of our beloved Prof. Giovanni Morrone.
JournalGenes and Diseases
Except where otherwise noted, this item's license is described as This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).