Luding癌癥研究中心，霍華休斯醫(yī)學研究所,，德州大學西南分校醫(yī)學中心的研究者在最新的Science上發(fā)表細胞癌變的研究成果，Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells,。

腫瘤發(fā)生是個極其復雜的過程,，當中牽涉多種基因多種轉錄因子，以及一些表觀遺傳學的突變,。世人卻忽視了細胞外在的環(huán)境變化,，究竟是哪種外在的變化會激起細胞發(fā)生深刻的變化，導致癌變,？

研究發(fā)現(xiàn),，結腸癌和直腸癌細胞常常伴隨KRAS或BRAF的突變，深入分析發(fā)現(xiàn),，兩個基因變異的過程中伴隨GLUT1的高表達,，GLUT1是編碼葡萄糖轉換子1的基因,。發(fā)生癌變的細胞中GLUT1都表現(xiàn)出GLUT1的高表達。癌變細胞對葡萄糖的攝入升高,，并且葡萄糖的酵解也加速,，這些癌細胞適應存活在這種低糖環(huán)境下。

這些研究數(shù)據(jù)表明,，葡萄糖缺乏是促使KRAS信號通路變異的外在環(huán)境,，腫瘤細胞就在這樣的環(huán)境中滋生。（生物谷Bioon.com）

生物谷推薦原始出處：

Science August 6, 2009 DOI: 10.1126/science.1174229

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

1 The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Batimore, MD 21231, USA.
2 The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Batimore, MD 21231, USA. ; Present address: Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
3 The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Batimore, MD 21231, USA.; Present address: Cardiovascular Medicine Brigham and Women’s Hospital, Boston, MA 02115, USA.
4 Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
5 Department of Medicine and Ireland Cancer Center, Case Western Reserve University and Case Medical Center of University Hospitals of Cleveland and Howard Hughes Medical Institute, Cleveland, OH 44106, USA.
6 The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Batimore, MD 21231, USA.; Present address: Sanofi-Aventis, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.

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.