作者
Ubaldo E Martinez-Outschoorn, Joseph M Curry, Ying-Hui Ko, Zhao Lin, Madalina Tuluc, David Cognetti, Ruth C Birbe, Edmund Pribitkin, Alessandro Bombonati, Richard G Pestell, Anthony Howell, Federica Sotgia, Michael P Lisanti
发表日期
2013/8/15
期刊
Cell cycle
卷号
12
期号
16
页码范围
2580-2597
出版商
Taylor & Francis
简介
Here, we developed a model system to evaluate the metabolic effects of oncogene(s) on the host microenvironment. A matched set of “normal” and oncogenically transformed epithelial cell lines were co-cultured with human fibroblasts, to determine the “bystander” effects of oncogenes on stromal cells. ROS production and glucose uptake were measured by FACS analysis. In addition, expression of a panel of metabolic protein biomarkers (Caveolin-1, MCT1, and MCT4) was analyzed in parallel. Interestingly, oncogene activation in cancer cells was sufficient to induce the metabolic reprogramming of cancer-associated fibroblasts toward glycolysis, via oxidative stress. Evidence for “metabolic symbiosis” between oxidative cancer cells and glycolytic fibroblasts was provided by MCT1/4 immunostaining. As such, oncogenes drive the establishment of a stromal-epithelial “lactate-shuttle”, to fuel the anabolic growth of …
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UE Martinez-Outschoorn, JM Curry, YH Ko, Z Lin… - Cell cycle, 2013