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The YAP/TAZ activation under low density, while confers apoptosis resistance, renders cancer cells sensitivity to ferroptosis. These findings establish YAP/TAZ and Hippo pathways as novel determinants of ferroptosis. Therefore, inducing ferroptosis may have therapeutic potential for YAP/TAZ-activated chemo-resistant and metastatic tumor cells. Reciprocally, various YAP/TAZ-targeting treatments under clinical development may confer ferroptosis resistance, limiting the therapeutic efficacy.Vesicle Protein Sorting 35 (VPS35) is a novel oncog