ArticleBMC cancer2014
MUC16 mucin (CA125) attenuates TRAIL-induced apoptosis by decreasing TRAIL receptor R2 expression and increasing c-FLIP expression.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- CA125-related tumor cell kinetics variables after chemotherapy in advanced ovarian cancer: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Pooled it
- MUC1 and MUC16: critical for immune modulation in cancer therapeutics.Frontiers in immunology · 2024Review
- Mucins and mucinous ovarian carcinoma: Development, differential diagnosis, and treatment.Heliyon · 2023Review
- Application of apoptosis-related genes in a multiomics-related prognostic model study of gastric cancer.Frontiers in genetics · 2022Article
- Comparison of proteolytic, cytotoxic and anticoagulant properties of chromatographically fractionated bromelain to un-fractionated bromelain.American journal of translational research · 2021Article
- Mucins as a New Frontier in Pulmonary Fibrosis.Journal of clinical medicine · 2019Review
- Article
- Serum CA125 and ascites leptin level ratio predicts baseline clinical resistance to first-line platinum-based treatment and poor prognosis in patients with high grade serous ovarian cancer.American journal of cancer research · 2019Article
- Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer.Journal of innate immunity · 2017Review
- Mesothelial cells interact with tumor cells for the formation of ovarian cancer multicellular spheroids in peritoneal effusions.Clinical & experimental metastasis · 2016Article
- C-terminus of MUC16 activates Wnt signaling pathway through its interaction with β-catenin to promote tumorigenesis and metastasis.Oncotarget · 2016Article
- Mesothelin's minimal MUC16 binding moiety converts TR3 into a potent cancer therapeutic via hierarchical binding events at the plasma membrane.Oncotarget · 2016Article
- Membrane-proximal TRAIL species are incapable of inducing short circuit apoptosis signaling: Implications for drug development and basic cytokine biology.Scientific reports · 2016Article
- Understanding the Unique Attributes of MUC16 (CA125): Potential Implications in Targeted Therapy.Cancer research · 2015Review
- Article
- Membrane proximal ectodomain cleavage of MUC16 occurs in the acidifying Golgi/post-Golgi compartments.Scientific reports · 2015Article
- Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells.Oncotarget · 2015Article
- The XIAP inhibitor Embelin enhances TRAIL-induced apoptosis in human leukemia cells by DR4 and DR5 upregulation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- MUC16 mucin (CA125) regulates the formation of multicellular aggregates by altering β-catenin signaling.American journal of cancer research · 2015Article
- Past, present and future targets for immunotherapy in ovarian cancer.Immunotherapy · 2014Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMUC16 (CA125) is a large transmembrane mucin protein (> 200 kDa) aberrantly expressed in approximately 80% of human epithelial ovarian cancers (EOC). MUC16 expression in EOC cells is associated with increased tumorigenesis and inhibiton of genotoxic drug-induced apoptosis. However, the mechanism by which MUC16 mediates these effects is unknown. In the present study, we investigated the mechanisms by which MUC16 attenuates TRAIL-induced apoptosis.
methodsMUC16 expression was down-regulated by stably expressing an anti-MUC16 single-chain antibody (scFv) targeted to the endoplasmic reticulum (ER), which prevents cell surface localization of MUC16 in OVCAR3 cells. We also generated a MUC16 C-terminal domain (MUC16CTD) construct that was stably expressed in MUC16 negative SKOV3 cells.
resultsWe show that MUC16 attenuates apoptosis, activation of caspase-8 and mitochondria activation in EOC cells in response to TRAIL. MUC16 decreases TRAIL receptor R2 (DR5) expression and inhibits pro-caspase-8 activation at the death-inducing signaling complex (DISC). MUC16CTD expression is sufficient to attenuate the TRAIL signaling cascade. MUC16 knockdown decreases caspase-8 inhibitor cFLIP mRNA levels, increases cFLIP degradation, and consequently increases TRAIL-induced apoptosis. Down-regulation of cFLIP following treatment of MUC16-expressing OVCAR3 cells with cFLIP siRNA also increases TRAIL-induced apoptosis.
conclusionsThese findings indicate that MUC16 protects EOC cells against TRAIL-induced apoptosis through multiple mechanisms including the blockade of TRAIL R2 expression and the regulation of cFLIP expression at both the transcriptional and the protein level.
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