Metabolomic analysis of her2-positive breast cancer cells

The distinctive nature of HER2-positive breast cancers is marked by overexpression of the HER2 receptor and little is known about the role of HER2 on cellular metabolism. Changes in metabolic flux are considered a common hallmark of cancers and can be traced to perturbations in gene expression. This study investigates the relationship between HER2 signaling and cellular metabolism in HER2-expressing cell lines, to test the hypothesis that metabolic profiles change with increasing HER2 positivity. A NMR-based metabolomics approach combined with interrogation of public gene expression databases was taken to compare the impact of metabolite and gene expression profiles of four human breast cancer cell lines under two experimental conditions: (1) varying HER2 expression, and (2) treatment with a broad-range phosphatase inhibitor. Data analyses reveal elevated levels of leucine and isoleucine that correlate with increasing HER2 expression. Accumulation of lactate was also seen with increasing HER2 expression consistent with a metabolic flux favoring glycolysis. And phosphatase treatment highlighted a role for two classes of phosphatases in HER2 signaling. This study demonstrates the utility for data-driven research towards biomarker discovery in human disease models.