飢餓状態がras突然変異を誘起する：Vogelstein研

Published Online August 6, 2009 Science

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Reports

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

Jihye Yun ¹, Carlo Rago ¹, Ian Cheong ¹, Ray Pagliarini ², Philipp Angenendt ¹, Harith Rajagopalan ³, Kerstin Schmidt ¹, James K. V. Wilson ⁴, Sandy Markowitz ⁵, Shibin Zhou ¹, Luis A. Diaz Jr.¹, Victor Velculescu ¹, Christoph Lengauer ⁶, Kenneth W. Kinzler ¹, Bert Vogelstein ^1*, Nickolas Papadopoulos ¹

Tumor progression is driven by genetic mutations, but little is known about the environmental conditions that select for these mutations. Studying the transcriptomes of paired colorectal cancer cell lines that differed only in the mutational status of their KRAS or BRAF genes, we found that GLUT1, encoding glucose transporter-1, was one of three genes consistently upregulated in cells with KRAS or BRAF mutations. The mutant cells exhibited enhanced glucose uptake and glycolysis and survived in low glucose conditions, phenotypes that all required GLUT1 expression. In contrast, when cells with wild-type KRAS alleles were subjected to a low glucose environment, very few cells survived. Most surviving cells expressed high levels of GLUT1, and 4% of these survivors had acquired new KRAS mutations. The glycolysis inhibitor 3-bromopyruvate preferentially suppressed the growth of cells with KRAS or BRAF mutations. Together, these data suggest that glucose deprivation can drive the acquisition of KRAS pathway mutations in human tumors.

KRAS or BRAF の相互排他的変異がともに影響を受ける（rasだけではないというのがミソのような気がする）とすれば、面白い。
低血糖のほうが不利なのか。疫学的には大腸癌に糖尿病は危険因子ではなかったけ・・・？？原本を読んでみたいな。