• Inicio
  • Resultados de la búsqueda
  • Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer.

Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer.

Nature cell biology (2020-04-02)
Xiaoguang Liu, Kellen Olszewski, Yilei Zhang, Esther W Lim, Jiejun Shi, Xiaoshan Zhang, Jie Zhang, Hyemin Lee, Pranavi Koppula, Guang Lei, Li Zhuang, M James You, Bingliang Fang, Wei Li, Christian M Metallo, Masha V Poyurovsky, Boyi Gan
RESUMEN

SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its low solubility, forcing cancer cells with high levels of SLC7A11 (SLC7A11high) to constitutively reduce cystine to the more soluble cysteine. This presents a significant drain on the cellular NADPH pool and renders such cells dependent on the pentose phosphate pathway. Limiting glucose supply to SLC7A11high cancer cells results in marked accumulation of intracellular cystine, redox system collapse and rapid cell death, which can be rescued by treatments that prevent disulfide accumulation. We further show that inhibitors of glucose transporters selectively kill SLC7A11high cancer cells and suppress SLC7A11high tumour growth. Our results identify a coupling between SLC7A11-associated cystine metabolism and the pentose phosphate pathway, and uncover an accompanying metabolic vulnerability for therapeutic targeting in SLC7A11high cancers.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
L-Glutamine-13C5, 98 atom % 13C, 95% (CP)
Sigma-Aldrich
Monoclonal Anti-Vinculin antibody produced in mouse, clone VIN-11-5, ascites fluid
Sigma-Aldrich
Phenazine ethosulfate, ≥95%
Sigma-Aldrich
trans-Androsterone
Sigma-Aldrich
BAY-876, ≥98% (HPLC)
Sigma-Aldrich
Glucose-6-phosphate Dehydrogenase from baker's yeast (S. cerevisiae), Type IX, lyophilized powder, 200-400 units/mg protein (modified Warburg-Christian)

Redes sociales

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

Merck

Investigación. Desarrollo. Producción.

Somos un proveedor líder para la industria de Ciencias de la Vida con soluciones y servicios para investigación, desarrollo y producción biotecnológicos, y para desarrollo y producción de tratamientos farmacéuticos

© 2021 Merck KGaA, Darmstadt, Alemania y/o sus filiales. Todos los derechos reservados.

Queda estrictamente prohibida la reproducción sin permiso de cualquiera de los materiales de la página web.