RB1-deficient prostate tumor growth and metastasis are vulnerable to ferroptosis induction via the E2F/ACSL4 axis.

ABSTRACT: Inactivation of the RB1 tumor suppressor gene is common in several types of therapy-resistant cancers, including metastatic castration-resistant prostate cancer, and predicts poor clinical outcomes. Effective therapeutic strategies against RB1-deficient cancers remain elusive. Here, we showed that RB1 loss/E2F activation sensitized cancer cells to ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, by upregulating expression of ACSL4 and enriching ACSL4-dependent arachidonic acid-containing phospholipids, which are key components of ferroptosis execution. ACSL4 appeared to be a direct E2F target gene and was critical to RB1 loss-induced sensitization to ferroptosis. Importantly, using cell line-derived xenografts and genetically engineered tumor models,

SUBMITTER: Wang ME 

PROVIDER: S-EPMC10178842 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature