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Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Author's view: epithelial plasticity metabolically reprograms normal cells towards a neoplastic-prone state
Hailun Wang1, Phuoc T Tran1,2,3
1Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Molecular & Cellular Oncology
|February 22, 2019
Summary
Epithelial plasticity reprograms lung cells metabolically by boosting the hexosamine biosynthetic pathway (HBP), increasing O-GlcNAcylation. This elevates Kras-driven lung tumorigenesis by suppressing tumor suppressor pathways.
Area of Science:
- Cellular metabolism
- Cancer biology
- Molecular glycosylation
Background:
- Epithelial plasticity is crucial for tissue repair and development.
- Metabolic reprogramming is a hallmark of cancer.
- Protein O-GlcNAcylation plays diverse roles in cellular signaling.
Purpose of the Study:
- To investigate the metabolic reprogramming of lung epithelial cells during plasticity.
- To determine the role of the hexosamine biosynthetic pathway (HBP) in lung tumorigenesis.
- To elucidate the impact of O-GlcNAcylation on oncogene-induced senescence and tumor suppressor pathways.
Main Methods:
- Analysis of gene expression changes in lung epithelial cells.
- Measurement of global protein O-GlcNAcylation levels.
- Assessment of tumor suppressor pathway activation and senescence.
- Evaluation of Kras-driven lung tumor development in a mouse model.
Main Results:
- Epithelial plasticity increases expression of key HBP genes (GFPT2, UAP1) in lung cells.
- Global protein O-GlcNAcylation is elevated due to metabolic reprogramming.
- Increased O-GlcNAcylation suppresses oncogene-induced senescence and tumor suppressor pathways.
- Accelerated Kras-driven lung tumorigenesis was observed.
Conclusions:
- Metabolic reprogramming via HBP activation and O-GlcNAcylation is a key mechanism in epithelial plasticity.
- Elevated O-GlcNAcylation promotes lung tumorigenesis by inhibiting senescence and tumor suppression.
- Targeting the HBP or O-GlcNAcylation may offer therapeutic strategies for lung cancer.
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