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Metabolomic probe uncovers energy misappropriation in primary tumors

Joshua Rabinowitz
Caroline Bartman, Ludwig Cancer Research Princeton
Caroline Bartman

A study led by Ludwig Princeton Director Joshua Rabinowitz and Caroline Bartman, a postdoc in his laboratory, measured the rates of glycolysis and the TCA cycle—cellular energy production processes—in normal mouse tissues, five primary tumor types and metastases using a quantitative method that involves labeling molecules with heavy isotopes and tracing their metabolic fates. The researchers used these data to calculate total rates of ATP production, a measure of how much usable energy was being produced in each tissue type. While 95% of ATP in healthy tissues comes from the TCA cycle, the absolute rates of energy production from that source or glycolysis have never quite been determined for malignant tissues. Josh, Caroline and their colleagues reported in a Nature paper in February that primary tumors, long assumed to make and consume large quantities of energy, actually convert nutrients to usable energy at relatively low rates. This was not true, however, for lung metastases of breast cancer. Malignant tissues, the researchers propose, support their abnormal cell proliferation in part by neglecting energy investments in previously normal tissue functions. In the pancreatic tumor model, for example, the cancer cells scavenged the energy they needed for proliferation by slowing down protein synthesis, a major energy-hog in the healthy tissue. The findings have implications for therapies that seek to starve tumors to stall their growth.

Slow TCA flux and ATP production in primary solid tumours but not metastases
Nature, 2023 February 1

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