ArticleFrontiers in oncology2024
E2F1 mediates competition, proliferation and response to cisplatin in cohabitating resistant and sensitive ovarian cancer cells.
Article in Frontiers in oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 6 citations in OpenAlex.
- Decoding the association between platinum resistance and HPV status in cervical cancer using organoid models.BMC biology · 2026Article
- Oleic acid fuels cisplatin-resistant ovarian cancer through FABP4-driven lipid uptake.Molecular metabolism · 2026Article
- A Systematic Review of Evidence for the Cost of Therapeutic Resistance in Cancer.bioRxiv : the preprint server for biology · 2025Article
- TIMP1 Overexpression in Ovarian Cancer Spheroids: Implications for Prognosis, Resistance, and Metastatic Potential.Cancers · 2025Article
- Complement activation at the interface between adipocytes and cancer cells drives tumor progression.JCI insight · 2025Article
- Differential PARP inhibitor responses in BRCA1-deficient and resistant cells in competitive co-culture.PloS one · 2025Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Background: Tumor heterogeneity is one of the key factors leading to chemo-resistance relapse. It remains unknown how resistant cancer cells influence sensitive cells during cohabitation and growth within a heterogenous tumors. The goal of our study was to identify driving factors that mediate the interactions between resistant and sensitive cancer cells and to determine the effects of cohabitation on both phenotypes. Methods: We used isogenic ovarian cancer (OC) cell lines pairs, sensitive and resistant to platinum: OVCAR5 vs. OVCAR5 CisR and PE01 vs. PE04, respectively, to perform long term direct culture and to study the phenotypical changes of the interaction of these cells. Results: Long term direct co-culture of sensitive and resistant OC cells promoted proliferation (p < 0.001) of sensitive cells and increased the proportion of cells in the G1 and S cell cycle phase in both PE01 and OVCAR5 cells. Direct co-culture led to a decrease in the IC50 to platinum in the cisplatin-sensitive cells (5.92 µM to 2.79 µM for PE01, and from 2.05 µM to 1.51 µM for OVCAR5). RNAseq analysis of co-cultured cells showed enrichment of Cell Cycle Control, Cyclins and Cell Cycle Regulation pathways. The transcription factor E2F1 was predicted as the main effector responsible for the transcriptomic changes in sensitive cells. Western blot and qRT-PCR confirmed upregulation of E2F1 in co-cultured vs monoculture. Furthermore, an E2F1 inhibitor reverted the increase in proliferation rate induced by co-culture to baseline levels. Conclusion: Our data suggest that long term cohabitation of chemo-sensitive and -resistant cancer cells drive sensitive cells to a higher proliferative state, more responsive to platinum. Our results reveal an unexpected effect caused by direct interactions between cancer cells with different proliferative rates and levels of platinum resistance, modelling competition between cells in heterogeneous tumors.
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