ArticlePloS one2010
Oncoproteomic analysis reveals co-upregulation of RELA and STAT5 in carboplatin resistant ovarian carcinoma.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review.Frontiers in physiology · 2021Pooled it
- TCM Treatment of Endometriosis: Pathogenesis, Mechanism and Clinical Practice.Drug design, development and therapy · 2026Review
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- Decoding early-onset of colorectal cancer: Insights into SERPINA3 expression patterns.Heliyon · 2024Article
- Proteomic landscape of epithelial ovarian cancer.Nature communications · 2024Article
- Review
- Multiparameter single-cell proteomic technologies give new insights into the biology of ovarian tumors.Seminars in immunopathology · 2023Review
- Computational drug repositioning for the identification of new agents to sensitize drug-resistant breast tumors across treatments and receptor subtypes.Frontiers in oncology · 2023Article
- Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening.Drug design, development and therapy · 2023Article
- Synthesis and Structural Characterization of Novel Trihalo-sulfone Inhibitors of WNK1.ACS medicinal chemistry letters · 2022Article
- Review
- A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells.International journal of molecular sciences · 2022Review
- In-depth analysis of the expression and functions of signal transducers and activators of transcription in human ovarian cancer.Frontiers in oncology · 2022Article
- Exploring the clinical value of tumor microenvironment in platinum-resistant ovarian cancer.Seminars in cancer biology · 2021Review
- High-grade serous tubo-ovarian cancer refined with single-cell RNA sequencing: specific cell subtypes influence survival and determine molecular subtype classification.Genome medicine · 2021Article
- Differential gene expression in peritumoral brain zone of glioblastoma: role of SERPINA3 in promoting invasion, stemness and radioresistance of glioma cells and association with poor patient prognosis and recurrence.Journal of neuro-oncology · 2021Article
- Review
- The Origin and Pathogenesis of Endometriosis.Annual review of pathology · 2020Review
- Targeting the PI3K/AKT/mTOR/NFκB Axis in Ovarian Cancer.Journal of cellular immunology · 2020Article
- Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity.Cancers · 2019Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundOvarian cancer is one of the most lethal types of female malignancy. Although most patients are initially responsive to platinum-based chemotherapy, almost all develop recurrent chemoresistant tumors and succumb to their diseases. Elucidating the pathogenesis underlying drug resistance is fundamental to the development of new therapeutics, leading to improved clinical outcomes in these patients. METHODS AND
findingsWe compared the proteomes of paired primary and recurrent post-chemotherapy ovarian high-grade serous carcinomas from nine ovarian cancer patients using CIEF/Nano-RPLC coupled with ESI-Tandem MS. As compared to their primary tumors, more than half of the recurrent tumors expressed higher levels of several proteins including CP, FN1, SYK, CD97, AIF1, WNK1, SERPINA3, APOD, URP2, STAT5B and RELA (NF-kappaB p65), which were also validated by quantitative RT-PCR. Based on shRNA screening for the upregulated genes in in vitro carboplatin-resistant cells, we found that simultaneous knockdown of RELA and STAT5B was most effective in sensitizing tumor cells for carboplatin treatment. Similarly, the NF-kappaB inhibitor, BMS-345541, and the STAT5 inhibitor, Dasatinib, significantly enhanced cell sensitivity to carboplatin. Moreover, both RELA and STAT5 are known to bind to the promoter region of Bcl-X, regulating its promoter activity. In this regard, augmented Bcl-xL expression was detected in carboplatin-resistant cells. Combined ectopic expression of RELA and STAT5B enhanced Bcl-xL promoter activity while treatment with BMS-345541 and Dasatinib decreased it. Chromatin immunoprecipitation of the Bcl-X promoter region using a STAT5 antibody showed induction of RELA and STAT5 DNA-binding segments both in naïve cells treated with a high concentration of carboplatin as well as in carboplatin-resistant cells.
conclusionsProteomic analysis identified RELA and STAT5 as two major proteins associated with carboplatin resistance in ovarian tumors. Our results further showed that NF-kappaB and STAT5 inhibitor could sensitize carboplatin-resistant cells and suggest that such inhibitors can be used to benefit patients with carboplatin-resistant recurrent ovarian cancer.
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Registered trials
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