ArticleJournal of experimental & clinical cancer research : CR2017
FOXM1 expression is significantly associated with chemotherapy resistance and adverse prognosis in non-serous epithelial ovarian cancer patients.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 67 citations in OpenAlex.
- FOXM1 drives cisplatin resistance in ovarian cancer through STIM1-mediated SOCE and STAT1 activation.Molecular therapy. Oncology · 2026Article
- The Regulatory Network of FOXM1: Orchestrating Cancer Progression and Resistance to Therapy.International journal of molecular sciences · 2026Review
- FOXM1 induces therapy resistance and inhibits apoptosis in a variety of human cancers.Cell death & disease · 2026Review
- WTAP participates in the DNA damage response via an mCell death discovery · 2025Article
- New mechanism of miR-34a-5p in regulating the biological behavior of osteosarcoma by targeting FoxM1.Cytotechnology · 2025Article
- Druggable upregulated proteins in EWS-FLI-driven Ewing sarcoma as emerging new therapeutic targets.American journal of translational research · 2025Review
- Progress of targeted FOX family therapy in ovarian cancer.Frontiers in pharmacology · 2025Review
- Research progress on FOXM1 in ovarian cancer diagnosis and therapeutics.Frontiers in oncology · 2025Review
- PLK1 and FoxM1 expressions positively correlate in papillary thyroid carcinoma and their combined inhibition results in synergistic anti-tumor effects.Molecular oncology · 2024Article
- Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia's perspective.Frontiers in pharmacology · 2024Article
- FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.International journal of molecular sciences · 2023Review
- Foxm1 haploinsufficiency drives clonal hematopoiesis and promotes a stress-related transition to hematologic malignancy in mice.The Journal of clinical investigation · 2023Article
- FOXM1: A small fox that makes more tracks for cancer progression and metastasis.Seminars in cancer biology · 2023Review
- Domatinostat Targets the FOXM1-Survivin Axis to Reduce the Viability of Ovarian Cancer Cells Alone and in Combination with Chemotherapeutic Agents.International journal of molecular sciences · 2023Article
- A diagnostic miRNA panel to detect recurrence of ovarian cancer through artificial intelligence approaches.Journal of cancer research and clinical oncology · 2023Article
- T Cell-Mediated Tumor Killing-Related Classification of the Immune Microenvironment and Prognosis Prediction of Lung Adenocarcinoma.Journal of clinical medicine · 2022Article
- FAT10 promotes chemotherapeutic resistance in pancreatic cancer by inducing epithelial-mesenchymal transition via stabilization of FOXM1 expression.Cell death & disease · 2022Article
- Review
- Identification of a novel gene signature predicting response to first-line chemotherapy in BRCA wild-type high-grade serous ovarian cancer patients.Journal of experimental & clinical cancer research : CR · 2022Article
- Downregulation of lncRNAOncology reports · 2022Article
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Authors and funding
26 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundEpithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis across the three major EOC subtypes, and its role in tumorigenesis and chemo-resistance in vitro.
methodsGene signatures were generated by microarray for 14 clear-cell and 26 endometrioid EOCs, and 15 normal endometrium snap-frozen biopsies. Validation of FOXM1 expression was performed by RT-qPCR and immunohistochemistry in the same samples and additionally in 50 high-grade serous EOCs and in their most adequate normal controls (10 luminal fallopian tube and 20 ovarian surface epithelial brushings). Correlations of FOXM1 expression to clinic-pathological parameters and patients' prognosis were evaluated by Kaplan-Meier and Cox proportional-hazards analyses. OVCAR-3 and two novel deeply characterized EOC cell lines (EOC-CC1 and OSPC2, with clear-cell and serous subtype, respectively) were employed for in vitro studies. Effects of FOXM1 inhibition by transient siRNA transfection were evaluated on cell-proliferation, cell-cycle, colony formation, invasion, and response to conventional first- and second-line anticancer agents, and to the PARP-inhibitor olaparib. Gene signatures of FOXM1-silenced cell lines were generated by microarray and confirmed by RT-qPCR.
resultsA significant FOXM1 mRNA up-regulation was found in EOCs compared to normal controls. FOXM1 protein overexpression significantly correlated to serous histology (p = 0.001) and advanced FIGO stage (p = 0.004). Multivariate analyses confirmed FOXM1 protein overexpression as an independent indicator of worse disease specific survival in non-serous EOCs, and of shorter time to progression in platinum-resistant cases. FOXM1 downregulation in EOC cell lines inhibited cell growth and clonogenicity, and promoted the cytotoxic effects of platinum compounds, doxorubicin hydrochloride and olaparib. Upon FOXM1 knock-down in EOC-CC1 and OSPC2 cells, microarray and RT-qPCR analyses revealed the deregulation of several common and other unique subtype-specific FOXM1 putative targets involved in cell cycle, metastasis, DNA repair and drug response.
conclusionsFOXM1 is up-regulated in all three major EOCs subtypes, and is a prognostic biomarker and a potential combinatorial therapeutic target in platinum resistant disease, irrespective of tumor histology.
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