Inhibiting system x(C)(-) and glutathione biosynthesis - a potential Achilles' heel in mutant-p53 cancers

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    Author
    Clemons, NJ; Liu, DS; Duong, CP; Phillips, WA
    Date
    2017-01-01
    Source Title
    Molecular & cellular oncology
    Publisher
    TAYLOR & FRANCIS INC
    University of Melbourne Author/s
    Duong, Cuong; Clemons, Nicholas; Phillips, Wayne
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Surgery (St Vincent's)
    Metadata
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    Document Type
    Journal Article
    Citations
    Clemons, N. J., Liu, D. S., Duong, C. P. & Phillips, W. A. (2017). Inhibiting system x(C)(-) and glutathione biosynthesis - a potential Achilles' heel in mutant-p53 cancers. MOLECULAR & CELLULAR ONCOLOGY, 4 (5), https://doi.org/10.1080/23723556.2017.1344757.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257441
    DOI
    10.1080/23723556.2017.1344757
    NHMRC Grant code
    NHMRC/1120293
    Abstract
    Effective therapeutic strategies to target mutant tumor protein p53 (TP53, best known as p53) cancers remain an unmet medical need. We found that mutant p53 impairs the function of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, commonly known as NRF2), suppresses solute carrier family 7 member 11 (SLC7A11) expression, and diminishes cellular glutamate/cystine exchange. This decreases glutathione biosynthesis, resulting in redox imbalance. Mutant p53 tumors are thus inherently susceptible to further perturbations of the SLC7A11/glutathione axis.

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