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Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis.

Cell metabolism | 2019

Successful metastasis requires the co-evolution of stromal and cancer cells. We used stable isotope labeling of amino acids in cell culture coupled with quantitative, label-free phosphoproteomics to study the bidirectional signaling in ovarian cancer cells and human-derived, cancer-associated fibroblasts (CAFs) after co-culture. In cancer cells, the interaction with CAFs supported glycogenolysis under normoxic conditions and induced phosphorylation and activation of phosphoglucomutase 1, an enzyme involved in glycogen metabolism. Glycogen was funneled into glycolysis, leading to increased proliferation, invasion, and metastasis of cancer cells co-cultured with human CAFs. Glycogen mobilization in cancer cells was dependent on p38α MAPK activation in CAFs. In vivo, deletion of p38α in CAFs and glycogen phosphorylase inhibition in cancer cells reduced metastasis, suggesting that glycogen is an energy source used by cancer cells to facilitate metastatic tumor growth.

Pubmed ID: 30174305 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA193256
  • Agency: NCI NIH HHS, United States
    Id: P30 CA014599
  • Agency: NCI NIH HHS, United States
    Id: R00 CA168997
  • Agency: NCI NIH HHS, United States
    Id: P30 CA014236
  • Agency: NCI NIH HHS, United States
    Id: R01 CA169604
  • Agency: NCI NIH HHS, United States
    Id: R21 CA201963

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