Iron inhibits glioblastoma cell migration and polarization.
Ganesh ShenoySina KheirabadiZaman AtaieAurosman Pappus SahuKondaiah PalsaQuinn WadeChachrit KhunsriraksakulVladimir KhristovBecky Slagle-WebbJustin D LathiaHong-Gang WangAmir SheikhiJames R ConnorPublished in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2023)
Glioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent disease faced by most patients. Although research into the impact of iron on glioblastoma has addressed proliferation, there has been little investigation into how cellular iron impacts the ability of glioblastoma cells to migrate-a key question, especially in the context of the diffuse spread observed in these tumors. Herein, we show that increasing cellular iron content results in decreased migratory capacity of human glioblastoma cells. The decrease in migratory capacity was accompanied by a decrease in cellular polarization in the direction of movement. Expression of CDC42, a Rho GTPase that is essential for both cellular migration and establishment of polarity in the direction of cell movement, was reduced upon iron treatment. We then analyzed a single-cell RNA-seq dataset of human glioblastoma samples and found that cells at the tumor periphery had a gene signature that is consistent with having lower levels of cellular iron. Altogether, our results suggest that cellular iron content is impacting glioblastoma cell migratory capacity and that cells with higher iron levels exhibit reduced motility.
Keyphrases
- induced apoptosis
- single cell
- rna seq
- cell cycle arrest
- iron deficiency
- endothelial cells
- endoplasmic reticulum stress
- signaling pathway
- end stage renal disease
- oxidative stress
- chronic kidney disease
- cell migration
- cell death
- cell therapy
- mesenchymal stem cells
- bone marrow
- palliative care
- stem cells
- white matter
- peritoneal dialysis
- binding protein
- staphylococcus aureus
- cell cycle
- replacement therapy
- cerebral ischemia