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标题：SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway
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作者：Kun Fang ; Sha Du ; Dachuan Shen 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：7
页码：1-22
DOI：10.1016/j.isci.2022.104618
语种：English
出版社：Elsevier
摘要：SummaryFerroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Cancer cells differ in their sensitivity to ferroptosis. Here we showed that the Suppressor of fused homolog (SUFU), a critical component in Hedgehog signaling, regulates ferroptosis sensitivity of breast cancer cells. Ectopic SUFU expression suppressed, whereas depletion of SUFU enhanced the sensitivity of breast cancer cells to RSL3-triggered ferroptosis through deregulation of ACSL4. Moreover, SUFU depletion promoted the activation of Yes-associated protein (YAP), thereby increasing the expression of ACSL4. Mechanistically, SUFU is associated with LATS1. Deletion of a region comprising residues 174–385 in SUFU disrupted SUFU binding to LATS1, thus abrogating SUFU-mediated downregulation of the YAP-ACSL4 axis and sensitivity to ferroptosis. Noteworthy, we showed that vincristine downregulated SUFU, thus increasing breast cancer cell sensitivity to RSL3in vitroandin vivo. Together, our findings uncover SUFU as a novel regulator in ferroptosis sensitivity.Graphical abstractDisplay OmittedHighlights•SUFU regulates the sensitivity of breast cancer cells to ferroptosis•SUFU associates with LATS1 to downregulate the YAP-ACSL4 axis•Vincristine targets the SUFU-YAP-ACSL4 axisCell biology; Functional aspects of cell biology; Cancer