SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway.

ABSTRACT: Ferroptosis 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

SUBMITTER: Fang K 

PROVIDER: S-EPMC9253713 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature