AI Article Synopsis
- Metabolic changes are crucial for the growth of tumor cells, but the processes behind how tumors start, especially in colorectal cancer (CRC), are not well understood.
- In early stages of CRC, there is a specific increase in glycolysis and a decrease in a protein called mitochondrial pyruvate carrier (MPC), which plays a key role in linking glycolysis to glucose metabolism in mitochondria.
- Studies show that inhibiting MPC leads to more tumors in mouse models, indicating that the regulation of pyruvate metabolism is vital for starting cancer development.
Article Abstract
Although metabolic adaptations have been demonstrated to be essential for tumor cell proliferation, the metabolic underpinnings of tumor initiation are poorly understood. We found that the earliest stages of colorectal cancer (CRC) initiation are marked by a glycolytic metabolic signature, including downregulation of the mitochondrial pyruvate carrier (MPC), which couples glycolysis and glucose oxidation through mitochondrial pyruvate import. Genetic studies in Drosophila suggest that this downregulation is required because hyperplasia caused by loss of the Apc or Notch tumor suppressors in intestinal stem cells can be completely blocked by MPC overexpression. Moreover, in two distinct CRC mouse models, loss of Mpc1 prior to a tumorigenic stimulus doubled the frequency of adenoma formation and produced higher grade tumors. MPC loss was associated with a glycolytic metabolic phenotype and increased expression of stem cell markers. These data suggest that changes in cellular pyruvate metabolism are necessary and sufficient to promote cancer initiation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004878 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2019.11.002 | DOI Listing |
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