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- Wang, Y, et al.
(författare)
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Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer
- 2022
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 29:11, s. 2190-2202
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Tidskriftsartikel (refereegranskat)abstract
- The development of chemotherapy resistance is the most vital obstacle to clinical efficacy in gastric cancer (GC). The dysregulation of the Wnt/beta-catenin signaling pathway is critically associated with GC development and chemotherapy resistance. Ferroptosis is a form of regulated cell death, induced by an iron-dependent accumulation of lipid peroxides during chemotherapy. However, whether the Wnt/beta-catenin signaling directly controls resistance to cell death, remains unclear. Here, we show that the activation of the Wnt/beta-catenin signaling attenuates cellular lipid ROS production and subsequently inhibits ferroptosis in GC cells. The beta-catenin/TCF4 transcription complex directly binds to the promoter region of GPX4 and induces its expression, resulting in the suppression of ferroptotic cell death. Concordantly, TCF4 deficiency promotes cisplatin-induced ferroptosis in vitro and in vivo. Thus, we demonstrate that the aberrant activation of the Wnt/beta-catenin signaling confers ferroptosis resistance and suggests a potential therapeutic strategy to enhance chemo-sensitivity for advanced GC patients.
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- Zhang, HY, et al.
(författare)
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RNA Interference with chemically modified siRNA
- 2006
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Ingår i: Current topics in medicinal chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266. ; 6:9, s. 893-900
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Tidskriftsartikel (refereegranskat)
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