ArticleCell death & disease2021
The Smac mimetic BV6 cooperates with STING to induce necroptosis in apoptosis-resistant pancreatic carcinoma cells.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Review
- Bidirectional Crosstalk Between cGAS-STING and Necroptosis: From Mitochondrial DNA Release to Inflammatory Disease.Drug design, development and therapy · 2026Review
- Transition between cell states of sensitivity reveals molecular vulnerability of drug-tolerant cells.Molecular systems biology · 2025Article
- Cracking the code of cancer immunotherapy resistance: emerging roles of pyroptosis and necroptosis.Journal of experimental & clinical cancer research : CR · 2025Review
- Uncovering the rewired IAP-JAK regulatory axis as an immune-dependent vulnerability of LKB1-mutant lung cancer.Nature communications · 2025Article
- Integrating bioinformatics and experimental validation to Investigate IRF1 as a novel biomarker for nucleus pulposus cells necroptosis in intervertebral disc degeneration.Scientific reports · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- A comparative study of apoptosis, pyroptosis, necroptosis, and PANoptosis components in mouse and human cells.PloS one · 2024Article
- 4-Deoxy-Drug design, development and therapy · 2024Article
- Genome, Metabolism, or Immunity: Which Is the Primary Decider of Pancreatic Cancer Fate through Non-Apoptotic Cell Death?Biomedicines · 2023Review
- Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells.Communications biology · 2023Article
- A panel of necroptosis-related genes predicts the prognosis of pancreatic adenocarcinoma.Translational oncology · 2022Article
- SBP-0636457, a Novel Smac Mimetic, Cooperates with Doxorubicin to Induce Necroptosis in Breast Cancer Cells during Apoptosis Blockage.Journal of oncology · 2022Article
- cGAS-STING pathway targeted therapies and their applications in the treatment of high-grade glioma.F1000Research · 2022Review
- The role of necroptosis in disease and treatment.MedComm · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer (PC) still remains a major cause of cancer-related death worldwide and alternative treatments are urgently required. A common problem of PC is the development of resistance against apoptosis that limits therapeutic success. Here we demonstrate that the prototypical Smac mimetic BV6 cooperates with the stimulator of interferon (IFN) genes (STING) ligand 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) to trigger necroptosis in apoptosis-deficient PC cells. Pharmacological inhibition of key components of necroptosis signaling, such as receptor-interacting protein 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL), significantly rescues PC cells from 2'3'-cGAMP/BV6/zVAD.fmk-mediated cell death, suggesting the induction of necroptosis. Consistently, 2'3'-cGAMP/BV6 co-treatment promotes phosphorylation of MLKL. Furthermore, we show that 2'3'-cGAMP stimulates the production of type I IFNs, which cooperate with BV6 to trigger necroptosis in apoptosis-deficient settings. STING silencing via siRNA or CRISPR/Cas9-mediated gene knockout protects PC cells from 2'3'-cGAMP/BV6/zVAD.fmk-mediated cell death. Interestingly, we demonstrate that nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNFα), and IFN-regulatory factor 1 (IRF1) signaling are involved in triggering 2'3'-cGAMP/BV6/zVAD.fmk-induced necroptosis. In conclusion, we show that activated STING and BV6 act together to exert antitumor effects on PC cells with important implications for the design of new PC treatment concepts.
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