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Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin

Author

Listed:
  • A. Flores

    (UCLA
    Broad Center for Regenerative Medicine, UCLA
    University of Southern California)

  • S. Sandoval-Gonzalez

    (UCLA)

  • R. Takahashi

    (UCLA)

  • A. Krall

    (UCLA)

  • L. Sathe

    (UCLA)

  • L. Wei

    (UCLA)

  • C. Radu

    (UCLA)

  • J. H. Joly

    (USC
    University of Southern California)

  • N. A. Graham

    (USC
    University of Southern California
    University of Southern California)

  • H. R. Christofk

    (UCLA
    UCLA
    Molecular Biology Institute, UCLA
    Jonsson Comprehensive Cancer Center, UCLA)

  • W. E. Lowry

    (UCLA
    Broad Center for Regenerative Medicine, UCLA
    UCLA
    Molecular Biology Institute, UCLA)

Abstract

Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers.

Suggested Citation

  • A. Flores & S. Sandoval-Gonzalez & R. Takahashi & A. Krall & L. Sathe & L. Wei & C. Radu & J. H. Joly & N. A. Graham & H. R. Christofk & W. E. Lowry, 2019. "Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07857-9
    DOI: 10.1038/s41467-018-07857-9
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