ArticleNeoplasia (New York, N.Y.)2010
c-Met overexpression contributes to the acquired apoptotic resistance of nonadherent ovarian cancer cells through a cross talk mediated by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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64 citing papers in PubMed, 111 citations in OpenAlex.
- c-Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine.Journal of veterinary internal medicine · 2018Trial
- Critical roles of Hedgehog signaling pathway in regulating the multidrug resistance of ovarian cancer.Journal of ovarian research · 2026Review
- Cisplatin as a Xenobiotic Agent: Molecular Mechanisms of Actions and Clinical Applications in Oncology.Journal of xenobiotics · 2026Review
- Beyond tumor‑associated macrophages involved in spheroid formation and dissemination: Novel insights for ovarian cancer therapy (Review).International journal of oncology · 2024Review
- MET overexpression in ovarian cancer via CD24-induced downregulation of miR-181a: A signalling for cellular quiescence-like state and chemoresistance in ovarian CSCs.Cell proliferation · 2024Article
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 Is Associated with Aggressive Epithelial Ovarian Cancer.Biomedicines · 2022Article
- Article
- The levels of soluble cMET ectodomain in the blood of patients with ovarian cancer are an independent prognostic biomarker.Molecular oncology · 2021Article
- FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation.Cell death & disease · 2021Article
- Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.Molecular carcinogenesis · 2021Article
- The role of MET in chemotherapy resistance.Oncogene · 2021Review
- Identification and Functional Validation of Differentially Expressed microRNAs in Ascites-Derived Ovarian Cancer Cells Compared with Primary Tumour Tissue.Cancer management and research · 2021Article
- BRN2 expression increases anoikis resistance in melanoma.Oncogenesis · 2020Article
- Molecular determinants of response to PI3K/akt/mTOR and KRAS pathways inhibitors in NSCLC cell lines.American journal of cancer research · 2020Article
- Crizotinib and PARP inhibitors act synergistically by triggering apoptosis in high-grade serous ovarian cancer.Oncotarget · 2019Article
- Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF.Cancer immunology research · 2019Article
- Tanshinone IIA induces apoptosis of ovarian cancer cellsOncology letters · 2019Article
- Development and validation of an immune gene-set based Prognostic signature in ovarian cancer.EBioMedicine · 2019Article
- Prognostic impact of high c-Met expression in ovarian cancer: a meta-analysis.Journal of Cancer · 2018Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer is the most lethal gynecologic cancer mainly because of widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis), which also underlies their resistance to chemotherapy. Here, we used a nonadherent cell culture model to investigate the molecular mechanisms of apoptotic resistance of ovarian cancer cells that may mimic the chemoresistance found in solid tumors. We found that ovarian cancer cells acquired a remarkable resistance to anoikis and apoptosis induced by exposure to clinically relevant doses of two front-line chemotherapeutic drugs cisplatin and paclitaxel when grown in three-dimensional than monolayer cultures. Inhibition of the hepatocyte growth factor (HGF) receptor c-Met, which is frequently overexpressed in ovarian cancer, by a specific inhibitor or small interfering RNA blocked the acquired anoikis resistance and restored chemosensitivity in three-dimensional not in two-dimensional cultures. These effects were found to be dependent on both phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) 1/2 signaling pathways. Inhibitors of PI3K/Akt abrogated ERK1/2 activation and its associated anoikis resistance in response to HGF, suggesting a signaling relay between these two pathways. Furthermore, we identified a central role of Ras as a mechanism of this cross talk. Interestingly, Ras did not lie upstream of PI3K/Akt, whereas PI3K/Akt signaling to ERK1/2 involved Ras. These findings shed new light on the apoptotic resistance mechanism of nonadherent ovarian cancer ascites cells and may have important clinical implications.
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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.