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

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...

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Detalles Bibliográficos
Autores principales: Clemons, Nicholas J., Liu, David S., Duong, Cuong P., Phillips, Wayne A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644480/
https://www.ncbi.nlm.nih.gov/pubmed/29057306
http://dx.doi.org/10.1080/23723556.2017.1344757
Descripción
Sumario: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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