Author's view: epithelial plasticity metabolically reprograms normal cells towards a neoplastic-prone state

Hailun Wang; Phuoc T Tran

doi:10.1080/23723556.2018.1543485

Author's view: epithelial plasticity metabolically reprograms normal cells towards a neoplastic-prone state

Mol Cell Oncol. 2018 Dec 24;6(1):1543485. doi: 10.1080/23723556.2018.1543485. eCollection 2019.

Authors

Hailun Wang¹, Phuoc T Tran^{1

2

3}

Affiliations

¹ Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

We have uncovered that epithelial plasticity programs metabolically reprogram epithelial lung cells by increasing expression of genes (e.g., glutamine-fructose-6-phosphate transaminase 2 - GFPT2 and UDP-N-acetylglucosamine pyrophosphorylase 1 - UAP1) critical for the hexosamine biosynthetic pathway (HBP) and elevating global protein O-GlcNAcylation - a specific type of glycosylation. We found that increased O-GlcNAcylation could suppress oncogene-induced senescence tumor suppressor pathways that ultimately led to accelerated Kras^G12D -driven lung tumorigenesis.

Keywords: O-GlcNAcylation; epithelial plasticity; epithelial-mesenchymal transition; hexosamine biosynthetic pathway; oncogene-induced senescence.

Abstract

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