ArticleCancer research2011
FOXO3a-Dependent Mechanism of E1A-Induced Chemosensitization.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- FOXO3a-interacting proteins' involvement in cancer: a review.Molecular biology reports · 2024Review
- Role and regulation of FOXO3a: new insights into breast cancer therapy.Frontiers in pharmacology · 2024Review
- Effects of resveratrol and its derivative pterostilbene on hepatic injury and immunological stress of weaned piglets challenged with lipopolysaccharide.Journal of animal science · 2022Article
- E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential.Frontiers in pharmacology · 2021Review
- Article
- A novel role mediated by adenoviral E1A in suppressing cancer through modulating decorin.Medical oncology (Northwood, London, England) · 2019Article
- Polyethylenimine (PEI)-Mediated E1A Increases the Sensitivity of Hepatocellular Carcinoma Cells to Chemotherapy.Medical science monitor basic research · 2019Article
- Adjudin synergizes with paclitaxel and inhibits cell growth and metastasis by regulating the sirtuin 3-Forkhead box O3a axis in human small-cell lung cancer.Thoracic cancer · 2019Article
- Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells.AIMS genetics · 2018Article
- Synergistic effect of bladder cancer-specific oncolytic adenovirus in combination with chemotherapy.Oncology letters · 2017Article
- The interaction between acetylation and serine-574 phosphorylation regulates the apoptotic function of FOXO3.Oncogene · 2017Article
- Expression of PH Domain Leucine-rich Repeat Protein Phosphatase, Forkhead Homeobox Type O 3a and RAD51, and their Relationships with Clinicopathologic Features and Prognosis in Ovarian Serous Adenocarcinoma.Chinese medical journal · 2017Article
- A novel application of E1A in combination therapy with EGFR-TKI treatment in breast cancer.Oncotarget · 2016Article
- Serine 574 phosphorylation alters transcriptional programming of FOXO3 by selectively enhancing apoptotic gene expression.Cell death and differentiation · 2016Article
- Forkhead Box Transcription Factor (FOXO3a) mediates the cytotoxic effect of vernodalin in vitro and inhibits the breast tumor growth in vivo.Journal of experimental & clinical cancer research : CR · 2015Article
- Targeting of TGF-β-activated protein kinase 1 inhibits chemokine (C-C motif) receptor 7 expression, tumor growth and metastasis in breast cancer.Oncotarget · 2015Article
- Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer.International journal of clinical and experimental pathology · 2015Article
- De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells.Oncotarget · 2014Article
- AMPK reverses the mesenchymal phenotype of cancer cells by targeting the Akt-MDM2-Foxo3a signaling axis.Cancer research · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Gene therapy trials in human breast, ovarian, and head and neck tumors indicate that adenovirus E1A can sensitize cancer cells to the cytotoxic effects of paclitaxel in vitro and in vivo. Resistance to paclitaxel has been reported to occur in cells expressing low levels of the Forkhead transcription factor FOXO3a. In this article, we report that FOXO3a is critical for E1A-mediated chemosensitization to paclitaxel. RNA interference-mediated knockdown of FOXO3a abolished E1A-induced sensitivity to paclitaxel. Mechanistic investigations indicated that E1A indirectly stabilized FOXO3a by acting at an intermediate step to inhibit a ubiquitin-dependent proteolysis pathway involving the E3 ligase βTrCP and the FOXO3a inhibitory kinase IKKβ. E1A derepressed this inhibitory pathway by stimulating expression of the protein phosphatase 2A (PP2A)/C protein phosphatases, which by binding to the TGF-β-activated kinase TAK1, inhibited its ability to activate IKKβ and, thereby, to suppress βTrCP-mediated degradation of FOXO3a. Thus, by stimulating PP2A/C expression, E1A triggers a signaling cascade that stabilizes FOXO3a and mediates chemosensitization. Our findings provide a leap forward in understanding paclitaxel chemosensitization by E1A, and offer a mechanistic rational to apply E1A gene therapy as an adjuvant for improving therapeutic outcomes in patients receiving paclitaxel treatment.
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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.