ArticleScientific reports2019
PAR-4 overcomes chemo-resistance in breast cancer cells by antagonizing cIAP1.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Epstein-Barr Virus-Mediated Apoptosis Evasion in Epithelial Malignancies: Molecular Mechanisms and Therapeutic Implications.Biology · 2026Review
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- Mechanistic insights into Rho/MRTF inhibition-induced apoptotic events and prevention of drug resistance in melanoma: implications for the involvement of pirin.Frontiers in pharmacology · 2025Article
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- The Landscape of Potential Targeted Treatments and Chemotherapy Efficacy Biomarkers for TNBC.Breast cancer (Dove Medical Press) · 2025Review
- Antitumor Efficacy of Arylquin 1 through Dose-Dependent Cytotoxicity, Apoptosis Induction, and Synergy with Radiotherapy in Glioblastoma Models.Biomedicines · 2024Article
- Evidence of direct interaction between cisplatin and the caspase-cleaved prostate apoptosis response-4 tumor suppressor.Protein science : a publication of the Protein Society · 2024Article
- Expression profiling of anticancer genes in colorectal cancer patients and their in vitro induction by riproximin, a ribosomal inactivating plant protein.Journal of cancer research and clinical oncology · 2023Article
- Anticancer genes (NOXA, PAR-4, TRAIL) are de-regulated in breast cancer patients and can be targeted by using a ribosomal inactivating plant protein (riproximin).Molecular biology reports · 2023Article
- Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance.Pharmaceuticals (Basel, Switzerland) · 2023Review
- DNMT3A governs tyrosine kinase inhibitors responses through IAPs and in a cell senescence-dependent manner in non-small cell lung cancer.American journal of cancer research · 2023Article
- UACA locus is associated with breast cancer chemoresistance and survival.NPJ breast cancer · 2022Article
- Pentagalloyl glucose inhibits TNF-α-activated CXCL1/GRO-α expression and induces apoptosis-related genes in triple-negative breast cancer cells.Scientific reports · 2021Article
- Prostate apoptosis response-4 and tumor suppression: it's not just about apoptosis anymore.Cell death & disease · 2021Review
- Connecting the Missing Dots: ncRNAs as Critical Regulators of Therapeutic Susceptibility in Breast Cancer.Cancers · 2020Review
- Caspase-8 knockdown suppresses apoptosis, while induces autophagy and chemo-sensitivity in non-small cell lung cancer cells.American journal of translational research · 2020Article
- AnBioTechniquesArticle
- Curcumin Sensitizes 4T1 Murine Breast Cancer Cells to Cisplatin Through PAR4 Secretion.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most deaths from breast cancer result from tumour recurrence, which is typically an incurable disease. Down-regulation of the pro-apoptotic tumour suppressor protein prostate apoptosis response-4 (PAR-4) is required for breast cancer recurrence and resistance to chemotherapy. Recent advances in the analysis of apoptotic signalling networks have uncovered an important role for activation of caspase-8 following DNA damage by genotoxic drugs. DNA damage induces depletion of IAP proteins and causes caspase-8 activation by promoting the formation of a cytosolic cell death complex. We demonstrate that loss of PAR-4 in triple negative breast cancer cell lines (TNBC) mediates resistance to DNA damage-induced apoptosis and prevents activation of caspase-8. Moreover, loss of PAR-4 prevents DNA damage-induced cIAP1 depletion. PAR-4 functions downstream of caspase-8 by cleavage-induced nuclear translocation of the C-terminal part and we demonstrate that nuclear translocation of the C-terminal PAR-4 fragment leads to depletion of cIAP1 and subsequent caspase-8 activation. Specifically targeting cIAP1 with RNAi or Smac mimetics (LCL161) overcomes chemo-resistance induced by loss of PAR-4 and restores caspase-8 activation. Our data identify cIAP1 as important downstream mediator of PAR-4 and we provide evidence that combining Smac mimetics and genotoxic drugs creates vulnerability for synthetic lethality in TNBC cells lacking PAR-4.
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