Desperately Seeking Glucose

Science Signaling  22 Sep 2009:
Vol. 2, Issue 89, pp. ec312
DOI: 10.1126/scisignal.289ec312

Mutations in oncogenes and tumor suppressor genes allow cancer cells to outgrow their neighboring healthy cells. What microenvironmental conditions provide a selective growth advantage to these cells? Yun et al. identify low glucose availability as a microenvironmental factor driving the acquisition of KRAS oncogenic mutations that allow cancer cells to survive and grow. In genetically matched colorectal cancer cells that differed only in the mutational status of the KRAS oncogene, mutant cells selectively overexpressed glucose transporter–1 and exhibited enhanced glucose uptake and glycolysis. When cells with wild-type KRAS were placed in a low-glucose environment, very few cells survived, but most of the survivors expressed high levels of glucose transporter–1 and a small percentage of the survivors had acquired new KRAS mutations. Thus, glucose deprivation may help to drive the acquisition of cell growth–promoting oncogenic mutations during tumor development.

J. Yun, C. Rago, I. Cheong, R. Pagliarini, P. Angenendt, H. Rajagopalan, K. Schmidt, J. K. V. Willson, S. Markowitz, S. Zhou, L. A. Diaz Jr., V. E. Velculescu, C. Lengauer, K. W. Kinzler, B. Vogelstein, N. Papadopoulos, Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325, 1555–1559 (2009). [Abstract] [Full Text]