Mutant GTF2I induces cell transformation and metabolic alterations in thymic epithelial cells.
In-Kyu KimGuanhua RaoXiaoliang ZhaoRuzong FanMaria Laura AvantaggiatiYisong WangYu-Wen ZhangGiuseppe GiacconePublished in: Cell death and differentiation (2020)
The pathogenesis of thymic epithelial tumors (TETs) is poorly understood. Recently we reported the frequent occurrence of a missense mutation in the GTF2I gene in TETs and hypothesized that GTF2I mutation might contribute to thymic tumorigenesis. Expression of mutant TFII-I altered the transcriptome of normal thymic epithelial cells and upregulated several oncogenic genes. Gtf2i L424H knockin cells exhibited cell transformation, aneuploidy, and increase tumor growth and survival under glucose deprivation or DNA damage. Gtf2i mutation also increased the expression of several glycolytic enzymes, cyclooxygenase-2, and caused modifications of lipid metabolism. Elevated cyclooxygenase-2 expression by Gtf2i mutation was required for survival under metabolic stress and cellular transformation of thymic epithelial cells. Our findings identify GTF2I mutation as a new oncogenic driver that is responsible for transformation of thymic epithelial cells.
Keyphrases
- poor prognosis
- dna damage
- single cell
- genome wide
- induced apoptosis
- cell therapy
- gene expression
- oxidative stress
- binding protein
- rna seq
- risk assessment
- stem cells
- bone marrow
- blood pressure
- signaling pathway
- cell cycle arrest
- cell death
- insulin resistance
- intellectual disability
- free survival
- nitric oxide synthase
- stress induced