ArticleMolecular oncology2020
Epithelial/mesenchymal heterogeneity of high-grade serous ovarian carcinoma samples correlates with miRNA let-7 levels and predicts tumor growth and metastasis.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- MRCKα represses GEF-H1 mediated RhoA activation to promote ovarian cancer spheroid growth and invasion.bioRxiv : the preprint server for biology · 2026Article
- Distinct origins of high-grade serous ovarian carcinoma: genetic and epigenetic evidence linking ovarian and fallopian tube epithelium to clinical outcomes and early detection.Molecular biology reports · 2025Review
- MORE interpretable multi-omic regulatory networks to characterise phenotypes.Briefings in bioinformatics · 2025Article
- From Defense to Disease: How the Immune System Fuels Epithelial-Mesenchymal Transition in Ovarian Cancer.International journal of molecular sciences · 2025Review
- miRNAs from Zebrafish Embryo Extracts Inhibit Breast Cancer Invasiveness and Migration by Modulating miR-218-5p/PI3K Pathway.International journal of molecular sciences · 2025Article
- Therapeutic Chemoresistance in Ovarian Cancer: Emerging Hallmarks, Signaling Mechanisms and Alternative Pathways.Current medicinal chemistry · 2025Review
- The microRNA Let-7 and its exosomal form: Epigenetic regulators of gynecological cancers.Cell biology and toxicology · 2024Review
- A Stem-like Patient-Derived Ovarian Cancer Model of Platinum Resistance Reveals Dissociation of Stemness and Resistance.International journal of molecular sciences · 2024Article
- Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers.International journal of molecular sciences · 2023Review
- E-Cadherin Expression in Relation to Clinicopathological Parameters and Survival of Patients with Epithelial Ovarian Cancer.International journal of molecular sciences · 2022Review
- Exosomes fromCancers · 2022Article
- CAF-Associated Paracrine Signaling Worsens Outcome and Potentially Contributes to Chemoresistance in Epithelial Ovarian Cancer.Frontiers in oncology · 2022Article
- TOP1 inhibition induces bifurcated JNK/MYC signaling that dictates cancer cell sensitivity.International journal of biological sciences · 2022Article
- Article
- Review
- The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer.Life (Basel, Switzerland) · 2021Article
- The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract.International journal of molecular sciences · 2021Review
- Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance.Nature communications · 2021Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patient-derived samples present an advantage over current cell line models of high-grade serous ovarian cancer (HGSOC) that are not always reliable and phenotypically faithful models of in vivo HGSOC. To improve upon cell line models of HGSOC, we set out to characterize a panel of patient-derived cells and determine their epithelial and mesenchymal characteristics. We analyzed RNA and protein expression levels in patient-derived xenograft (PDX) models of HGSOC, and functionally characterized these models using flow cytometry, wound healing assays, invasion assays, and spheroid cultures. Besides in vitro work, we also evaluated the growth characteristics of PDX in vivo (orthotopic PDX). We found that all samples had hybrid characteristics, covering a spectrum from an epithelial-to-mesenchymal state. Samples with a stronger epithelial phenotype were more active in self-renewal assays and more tumorigenic in orthotopic xenograft models as compared to samples with a stronger mesenchymal phenotype, which were more migratory and invasive. Additionally, we observed an inverse association between microRNA let-7 (lethal-7) expression and stemness, consistent with the loss of let-7 being an important component of the cancer stem cell phenotype. We observed that lower let-7 levels were associated with the epithelial state and a lower epithelial mesenchymal transition (EMT) score, more efficient spheroid and tumor formation, and increased sensitivity to platinum-based chemotherapy. Surprisingly, in these HGSOC cells, stemness could be dissociated from invasiveness: Cells with lower let-7 levels were more tumorigenic, but less migratory, and with a lower EMT score, than those with higher let-7 levels. We conclude that let-7 expression and epithelial/mesenchymal state are valuable predictors of HGSOC proliferation, in vitro self-renewal, and tumor burden in vivo.
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