ArticleClinical cancer research : an official journal of the American Association for Cancer Research2005
Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 113 citations in OpenAlex.
- Mutations in specific codons of the KRAS oncogene are associated with variable resistance to neoadjuvant chemoradiation therapy in patients with rectal adenocarcinoma.Annals of surgical oncology · 2013Trial
- FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages.Cell reports · 2026Article
- Ovarian Tumor FAK Inhibition Releases Omega-3 Fatty Acids Stimulating GATA6 Peritoneal Macrophage CXCL13 Production Enhancing Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Dual delivery of metformin and Y15 from a PLGA scaffold for the treatment of platinum-resistant ovarian cancer.Future medicinal chemistry · 2025Article
- Proapoptotic role of CDK1 in overcoming paclitaxel resistance in ovarian cancer cells in response to combined treatment with paclitaxel and duloxetine.Cancer cell international · 2024Article
- An In Vitro Analysis of TKI-Based Sequence Therapy in Renal Cell Carcinoma Cell Lines.International journal of molecular sciences · 2023Article
- RSPO2 promotes progression of ovarian cancer through dual receptor-mediated FAK/Src signaling activation.iScience · 2022Article
- Necroptosis-related lncRNA signature predicts prognosis and immune response for cervical squamous cell carcinoma and endocervical adenocarcinomas.Scientific reports · 2022Article
- The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes?Journal of experimental & clinical cancer research : CR · 2022Review
- IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells.Science signaling · 2022Article
- Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway.International journal of molecular sciences · 2022Article
- Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy.Molecules (Basel, Switzerland) · 2021Review
- The inhibition of BRAF activity sensitizes chemoresistant human ovarian cancer cells to paclitaxel-induced cytotoxicity and tumor growth inhibition.American journal of translational research · 2020Article
- Clinical significance of focal adhesion kinase (FAK) in cervical cancer progression and metastasis.International journal of clinical and experimental pathology · 2020Article
- Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy.Frontiers in molecular biosciences · 2019Review
- Article
- Inhibition of CDK4 sensitizes multidrug resistant ovarian cancer cells to paclitaxel by increasing apoptosiss.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- Inhibition of the integrin/FAK signaling axis and c-Myc synergistically disrupts ovarian cancer malignancy.Oncogenesis · 2017Article
- Erythropoietin Stimulates Tumor Growth via EphB4.Cancer cell · 2015Article
- Quinacrine promotes autophagic cell death and chemosensitivity in ovarian cancer and attenuates tumor growth.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveDocetaxel causes cell death through induction of apoptosis; however, cell death characteristics for docetaxel have not yet been fully elucidated. We examined the role of focal adhesion kinase (FAK) cleavage in docetaxel-mediated apoptosis.
methodsFAK degradation after treatment with docetaxel was determined in both taxane-sensitive (HeyA8 and SKOV3) and taxane-resistant (HeyA8-MDR and SKOV3-TR) ovarian cancer cell lines by Western blot analysis. Cell growth was determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. FAK-targeting small interfering RNA (siRNA) was used to decrease FAK expression. Apoptosis and caspase activity were determined using commercially available kits.
resultsSKOV3 and HeyA8 cell lines were both sensitive to docetaxel (IC50 levels, 1-6.2 nmol/L), whereas the SKOV3-TR and HeyA8-MDR cells were resistant (IC50>or=250 nmol/L for both). Docetaxel induced high rates of apoptosis in SKOV3 and HeyA8 cells (84% and 66% apoptosis, respectively) but minimal apoptosis (5-8%) in SKOV3-TR and HeyA8-MDR cells. Similarly, FAK was cleaved in SKOV3 and HeyA8 cells in response to docetaxel treatment but unchanged in the resistant cells. Caspase-3 and caspase-8 activity also increased significantly in docetaxel-treated SKOV3 and HeyA8 cells but not in the taxane-resistant cells. DEVD-fmk (caspase-3 blocker) was able to block both FAK cleavage and apoptosis mediated by docetaxel in SKOV3 and HeyA8 cells. FAK siRNA transfection resulted in 70% to 90% decrease in FAK levels in all cell lines within 72 hours. FAK silencing augmented docetaxel-mediated growth inhibition (5- to 8-fold increase) and apoptosis in both of the taxane-sensitive and taxane-resistant cell lines.
conclusionsDocetaxel induces FAK cleavage, mediated through activation of caspase-3, in taxane-sensitive ovarian cancer cells but not in taxane-resistant cells. The absence of FAK degradation may contribute to cell survival in taxane-resistant cells. FAK silencing promotes the in vitro efficacy of docetaxel in both taxane-sensitive and taxane-resistant cell lines and may serve as a novel therapeutic approach.
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