Journal Article

Mutant GTF2I induces cell transformation and metabolic alterations in thymic epithelial cells

Kim, In-Kyu, Zhang, Yu-Wen, Giaccone, Giuseppe, Avantaggiati, Maria Laura, Wang, Yisong, Rao, Guanhua, Fan, Ruzong, Zhao, Xiaoliang

2020

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/106 / 13/109 / 13/2 / 13/31 / 13/89 / 13/95 / 14/34 / 38/39 / 38/61 / 38/77 / 45/41 / 631/208/199 / 631/67/1857 / 631/67/395 / 82/58 / Aneuploidy / Apoptosis / Biochemistry / Biomedical and Life Sciences / Cell Biology / Cell Cycle Analysis / Cyclooxygenase-2 / DNA damage / Epithelial cells / Gene expression / Genetic transformation / Glycolysis / Life Sciences / Lipid metabolism / Metabolism / Missense mutation / Mutants / Mutation / Stem Cells / Thymus / Transcriptomes / Tumorigenesis