ArticleOncogene2004
Loss of XIAP protein expression by RNAi and antisense approaches sensitizes cancer cells to functionally diverse chemotherapeutics.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 170 citations in OpenAlex.
- Concomitance of downregulated active caspase-3 and upregulated X-chromosome linked inhibitor of apoptosis protein as a sensitive diagnostic approach for breast cancer.Molecular and cellular biochemistry · 2019Trial
- XIAP antisense oligonucleotide (AEG35156) achieves target knockdown and induces apoptosis preferentially in CD34+38- cells in a phase 1/2 study of patients with relapsed/refractory AML.Apoptosis : an international journal on programmed cell death · 2011Trial
- Simultaneous Inhibition of MDM2 and XIAP by MX69 Induced Cell Cycle Arrest and Apoptosis in HUH7 and Hep3B Cell Lines.Current issues in molecular biology · 2026Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Degradation of TRIM32 is induced by RTA for Kaposi's sarcoma-associated herpesvirus lytic replication.Journal of virology · 2024Article
- Article
- Apoptotic Effects of Anthocyanins fromInternational journal of molecular sciences · 2021Article
- The HECT E3 Ligase E6AP/UBE3A as a Therapeutic Target in Cancer and Neurological Disorders.Cancers · 2020Review
- Systematic mapping of cancer cell target dependencies using high-throughput drug screening in triple-negative breast cancer.Computational and structural biotechnology journal · 2020Article
- Co-expression of XIAP and CIAP1 Play Synergistic Effect on Patient's Prognosis in Head and Neck Cancer.Pathology oncology research : POR · 2019Article
- Casein Kinase 1 Delta Regulates Cell Proliferation, Response to Chemotherapy and Migration in Human Ovarian Cancer Cells.Frontiers in oncology · 2019Article
- Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment.Computational and structural biotechnology journal · 2019Review
- Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017Review
- microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of XIAP.British journal of cancer · 2017Article
- Targeting of X-linked inhibitor of apoptosis protein and PI3-kinase/AKT signaling by embelin suppresses growth of leukemic cells.PloS one · 2017Article
- The Gβ5 protein regulates sensitivity to TRAIL-induced cell death in colon carcinoma.Oncogene · 2015Article
- The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting of inhibitors of apoptosis.Oncotarget · 2014Article
- The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8.Cell death & disease · 2013Article
- Prognostic significance of XIAP and NF-κB expression in esophageal carcinoma with postoperative radiotherapy.World journal of surgical oncology · 2013Article
- RIP2 activity in inflammatory disease and implications for novel therapeutics.Journal of leukocyte biology · 2013Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stable expression of short-hairpin RNAs (shRNAs) directed against the X-linked inhibitor of apoptosis (XIAP) resulted in the generation of three MDA-MB-231 cell lines (XIAP shRNA cells) with reductions in XIAP mRNA and protein levels > 85% relative to MDA-MB-231 cells stably transfected with the U6 RNA polymerase III promoter alone (U6 cells). This RNA interference (RNAi) approach dramatically sensitized these cells to killing by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Importantly, loss of XIAP also sensitized the cells to killing by taxanes but had no additional effects on killing by carboplatin and doxorubicin. The increased sensitivity of the XIAP shRNA cells to killing by TRAIL and taxanes correlated with enhanced caspase cleavage and activation, including caspase-8, and robust processing of poly(ADP-ribose) polymerase and BID compared to U6 cells. Additionally, increasing XIAP levels by adenovirus-mediated expression protected both XIAP shRNA and U6 cells from TRAIL killing in a dose-dependent manner. The effects observed by stable RNAi with respect to TRAIL sensitization were also achieved following downregulation of XIAP in Panc-1 cells treated with a second-generation, mixed-backbone antisense oligonucleotide, AEG 35156/GEM640. These data indicate that reducing XIAP protein expression by either RNAi or antisense approaches increases cancer cell susceptibility to functionally diverse chemotherapeutic agents and supports the notion that downregulation of XIAP in vivo may synergize with disease-relevant chemotherapeutic regimes, including TRAIL and taxanes, to increase the effectiveness of antineoplastic agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.