ArticleJournal of the National Cancer Institute2011
Silencing of p130cas in ovarian carcinoma: a novel mechanism for tumor cell death.
Article in Journal of the National Cancer Institute, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Does tumour biology determine surgical success in the treatment of epithelial ovarian cancer? A systematic literature review.British journal of cancer · 2012Pooled it
- The p130Cas-Crk/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL.International journal of molecular sciences · 2025Review
- Hepatotoxicity of Nanoparticle-Based Anti-Cancer Drugs: Insights into Toxicity and Mitigation Strategies.International journal of nanomedicine · 2025Review
- Gallic acid in theabrownin suppresses cell proliferation and migration in non‑small cell lung carcinoma via autophagy inhibition.Oncology letters · 2023Article
- Dr.Nod: computational framework for discovery of regulatory non-coding drivers in tissue-matched distal regulatory elements.Nucleic acids research · 2023Article
- P130cas-FAK interaction is essential for YAP-mediated radioresistance of non-small cell lung cancer.Cell death & disease · 2022Article
- Novel germline mutation in lung cancer pedigrees establishesAnnals of translational medicine · 2022Article
- Endothelial p130cas confers resistance to anti-angiogenesis therapy.Cell reports · 2022Article
- Mutant TP53 interacts with BCAR1 to contribute to cancer cell invasion.British journal of cancer · 2021Article
- The interaction of p130Cas with PKN3 promotes malignant growth.Molecular oncology · 2019Article
- Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer.Annals of translational medicine · 2018Review
- Long Noncoding RNA in Cancer: Wiring Signaling Circuitry.Trends in cell biology · 2018Review
- The miR-24-3p/p130Cas: a novel axis regulating the migration and invasion of cancer cells.Scientific reports · 2017Article
- miR-509-3p is clinically significant and strongly attenuates cellular migration and multi-cellular spheroids in ovarian cancer.Oncotarget · 2016Article
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- Novel Axl-driven signaling pathway and molecular signature characterize high-grade ovarian cancer patients with poor clinical outcome.Oncotarget · 2015Article
- PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer.Molecular cancer therapeutics · 2015Article
- Review
- Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism.Molecular medicine reports · 2015Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundWe investigated the clinical and biological significance of p130cas, an important cell signaling molecule, in ovarian carcinoma.
methodsExpression of p130cas in ovarian tumors, as assessed by immunohistochemistry, was associated with tumor characteristics and patient survival. The effects of p130cas gene silencing with small interfering RNAs incorporated into neutral nanoliposomes (siRNA-DOPC), alone and in combination with docetaxel, on in vivo tumor growth and on tumor cell proliferation (proliferating cell nuclear antigen) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were examined in mice bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) or taxane-resistant (HeyA8-MDR) ovarian tumors (n = 10 per group). To determine the specific mechanisms by which p130cas gene silencing abrogates tumor growth, we measured cell viability (MTT assay), apoptosis (fluorescence-activated cell sorting), autophagy (immunoblotting, fluorescence, and transmission electron microscopy), and cell signaling (immunoblotting) in vitro. All statistical tests were two-sided.
resultsOf 91 ovarian cancer specimens, 70 (76%) had high p130cas expression; and 21 (24%) had low p130cas expression. High p130cas expression was associated with advanced tumor stage (P < .001) and higher residual disease (>1 cm) following primary cytoreduction surgery (P = .007) and inversely associated with overall survival and progression-free survival (median overall survival: high p130cas expression vs low expression, 2.14 vs 9.1 years, difference = 6.96 years, 95% confidence interval = 1.69 to 9.48 years, P < .001; median progression-free survival: high p130cas expression vs low expression, 1.04 vs 2.13 years, difference = 1.09 years, 95% confidence interval = 0.47 to 2.60 years, P = .01). In mice bearing orthotopically implanted HeyA8 or SKOV3ip1 ovarian tumors, treatment with p130cas siRNA-DOPC in combination with docetaxel chemotherapy resulted in the greatest reduction in tumor growth compared with control siRNA therapy (92%-95% reduction in tumor growth; P < .001 for all). Compared with control siRNA therapy, p130cas siRNA-DOPC reduced SKOV3ip1 cell proliferation (31% reduction, P < .001) and increased apoptosis (143% increase, P < .001) in vivo. Increased tumor cell apoptosis may have persisted despite pan-caspase inhibition by the induction of autophagy and related signaling pathways.
conclusionsIncreased p130cas expression is associated with poor clinical outcome in human ovarian carcinoma, and p130cas gene silencing decreases tumor growth through stimulation of apoptotic and autophagic cell death.
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Registered trials
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