ArticleCell death & disease2024
CRLF1 bridges AKT and mTORC2 through SIN1 to inhibit pyroptosis and enhance chemo-resistance in ovarian cancer.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Bifidobacterium longum engineered with artificial enzymes alleviates high-altitude colitis via inhibition of GPD2-dependent ferroptosis.Protoplasma · 2026Article
- Single-cell multiomic analysis of mesenchymal cells reveals molecular signatures and regulators of lung allograft fibrosis.JCI insight · 2026Article
- Non-canonical role of "S6K1-SGK1" pathway in neuronal necroptosis following traumatic brain injury.Genes & diseases · 2026Article
- Single-cell and multi-omics integration delineates the landscape of gene-wise intratumor heterogeneity and identifies prognostic biomarkers for immunotherapy in non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- MYBL2 impedes cisplatin sensitivity through suppressing GSDME-mediated pyroptosis in lung adenocarcinoma.Cell death discovery · 2026Article
- CRLF1 Drives Prostate Cancer Progression via COMP-Mediated Activation of the FAK/PI3K/AKT Signaling Pathway.Cancers · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Mitochondrial LINC01133 regulates pyroptosis and calcium homeostasis in cisplatin-resistant lung adenocarcinoma.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- GLUT3 drives paclitaxel resistance in peritoneal metastatic gastric cancer by promoting H3K18 lactylation-mediated MAPKAP1 transcription to suppress ferroptosis.International journal of biological sciences · 2026Article
- The role of pyroptosis in ovarian cancer.Discover oncology · 2025Review
- Phosphorylation of USP33 by CDK1 stabilizes the mTORC2 component SIN1.Cell death & disease · 2025Article
- LncRNA16 inhibits pyroptosis and promotes platinum resistance in non-small cell lung cancer by sponging miRNA1827 to regulate MBD3/GSDME expression.Cancer cell international · 2025Article
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Authors and funding
10 authors.
Funding
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Abstract
Ovarian cancer, the second most leading cause of gynecologic cancer mortality worldwide, is challenged by chemotherapy resistance, presenting a significant hurdle. Pyroptosis, an inflammation-linked programmed cell death mediated by gasdermins, has been shown to impact chemoresistance when dysregulated. However, the mechanisms connecting pyroptosis to chemotherapy resistance in ovarian cancer are unclear. We found that cytokine receptor-like factor 1 (CRLF1) is a novel component of mTORC2, enhancing AKT Ser473 phosphorylation through strengthening the interaction between AKT and stress-activated protein kinase interacting protein 1 (SIN1), which in turn inhibits the mitogen-activated protein kinase kinase kinase 5 (ASK1)-JNK-caspase-3-gasdermin E pyroptotic pathway and ultimately confers chemoresistance. High CRLF1-expressing tumors showed sensitivity to AKT inhibition but tolerance to cisplatin. Remarkably, overexpression of binding-defective CRLF1 variants impaired AKT-SIN1 interaction, promoting pyroptosis and chemosensitization. Thus, CRLF1 critically regulates chemoresistance in ovarian cancer by modulating AKT/SIN1-dependent pyroptosis. Binding-defective CRLF1 variants could be developed as tumor-specific polypeptide drugs to enhance chemotherapy for ovarian cancer.
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