Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells

• DOI: 10.1126/science.1174229
• Publication Date: 2009-08-07T01:55:26Z
• Authors: Jihye Yun; Carlo Rago; Ian Cheong; Ray Pagliarini; Philipp Angenendt; Harith Rajagopalan; Kerstin Schmidt; James K. V. Willson; Sandy Markowitz; Shibin Zhou; Luis A. Diaz; Victor E. Velculescu; Christoph Lengauer; Kenneth W. Kinzler; Bert Vogelstein; Nickolas Papadopo...
• Keywords: Proto-Oncogene Proteins B-raf; 0301 basic medicine; Glucose Transporter Type 1; Transplantation, Heterologous; Mice, Nude; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Genes, ras; Glucose; Cell Line, Tumor; Gene Targeting; Mutation; Animals; Humans; Lactic Acid; Colorectal Neoplasms; Pyruvates; Glycolysis; Neoplasm Transplantation; Cell Proliferation; Oligonucleotide Array Sequence Analysis

Desperately Seeking Glucose Mutations in oncogenes and tumor suppressor genes allow cancer cells to outgrow their neighboring healthy cells. What microenvironmental conditions provide a selective growth advantage these cells? Yun et al. (p. 1555 , published online 6 August) identify low glucose availability as factor driving the acquisition of KRAS oncogenic mutations that survive grow. In genetically matched colorectal differed only mutational status oncogene, mutant selectively overexpressed transporter-1 exhibited enhanced uptake glycolysis. When with wild-type were placed low-glucose environment, very few survived but most survivors expressed high levels transporter-1, small percentage had acquired new mutations. Thus, deprivation may help drive cell growth–promoting during development.