Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways.

ABSTRACT: There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. Unexpectedly a

SUBMITTER: Onodera Y 

PROVIDER: S-EPMC3871217 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature