NCOA4-Mediated Ferritinophagy Is a Pancreatic Cancer Dependency via Maintenance of Iron Bioavailability for Iron-Sulfur Cluster Proteins

NCOA4 介导的铁蛋白吞噬作用是一种胰腺癌依赖性,通过维持铁硫簇蛋白的铁生物利用度实现

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作者:Naiara Santana-Codina, Maria Quiles Del Rey #, Kevin S Kapner #, Huan Zhang #, Ajami Gikandi, Callum Malcolm, Clara Poupault, Miljan Kuljanin, Kristen M John, Douglas E Biancur, Brandon Chen, Nupur K Das, Kristen E Lowder, Connor J Hennessey, Wesley Huang, Annan Yang, Yatrik M Shah, Jonathan A Nowak

Significance

Autophagy and iron metabolism are metabolic dependencies in PDAC. However, targeted therapies for these pathways are lacking. We identify NCOA4-mediated selective autophagy of ferritin ("ferritinophagy") as upregulated in PDAC. Ferritinophagy supports PDAC iron metabolism and thereby tumor progression and represents a new therapeutic target in PDAC. See related commentary by Jain and Amaravadi, p. 2023. See related article by Ravichandran et al., p. 2198. This article is highlighted in the In This Issue feature, p. 2007.

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