ArticleBreast cancer research : BCR2021
Sublethal doxorubicin promotes migration and invasion of breast cancer cells: role of Src Family non-receptor tyrosine kinases.
Article in Breast cancer research : BCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- A narrative review of metabolomics approaches in identifying biomarkers of doxorubicin-induced cardiotoxicity.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Effect of Ageratum fastigiatum on Viability, Migration and Proliferation of Breast Cancer Cells in 2D and 3D Culture Models.Applied biochemistry and biotechnology · 2026Article
- Extracellular condensates (ECs) are endogenous modulators of HIV transcription and latency reactivation.Molecular psychiatry · 2026Article
- The translation factor eIF4E is a key mediator of doxorubicin resistance: insights from a triple-negative breast cancer model.Scientific reports · 2026Article
- Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches.Drug delivery and translational research · 2025Review
- Mitochondrial ROS inhibition prevents doxorubicin-induced breast cancer cell migration and invasion.iScience · 2025Article
- Chemotherapy alters radiosensitivity and GRPR expression of prostate and breast cancer cells.EJNMMI research · 2025Article
- Tristetraprolin affects invasion-associated genes expression and cell motility in triple-negative breast cancer model.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Targeting drug resistance in breast cancer: the potential of miRNA and nanotechnology-driven delivery systems.Nanoscale advances · 2024Review
- Article
- The Role of AKR1B10 in Lung Cancer Malignancy Induced by Sublethal Doses of Chemotherapeutic Drugs.Cancers · 2024Article
- Biological function, topology, and quantification of plasma membrane Ceramide.Advances in biological regulation · 2024Review
- MMP-2 regulates Src activation via repression of the CHK/MATK tumor suppressor in osteosarcoma.Cancer reports (Hoboken, N.J.) · 2023Article
- Hypophyllanthin and Phyllanthin fromACS omega · 2023Article
- Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells.Journal of medicinal chemistry · 2023Article
- PLGA Nanoparticles Containing VCAM-1 Inhibitor Succinobucol and Chemotherapeutic Doxorubicin as Therapy against Primary Tumors and Their Lung Metastases.Pharmaceutics · 2023Article
- Therapeutic Potential of Nanomedicine in Management of Alzheimer's Disease and Glioma.International journal of nanomedicine · 2023Review
- ML216-Induced BLM Helicase Inhibition Sensitizes PCa Cells to the DNA-Crosslinking Agent Cisplatin.Molecules (Basel, Switzerland) · 2022Article
- Doxorubicin-Induced Platelet Activation and Clearance Relieved by Salvianolic Acid Compound: Novel Mechanism and Potential Therapy for Chemotherapy-Associated Thrombosis and Thrombocytopenia.Pharmaceuticals (Basel, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDoxorubicin (Dox) is a widely used chemotherapy, but its effectiveness is limited by dose-dependent side effects. Although lower Dox doses reduce this risk, studies have reported higher recurrence of local disease with no improvement in survival rate in patients receiving low doses of Dox. To effectively mitigate this, a better understanding of the adverse effects of suboptimal Dox doses is needed.
methodsEffects of sublethal dose of Dox on phenotypic changes were assessed with light and confocal microscopy. Migratory and invasive behavior were assessed by wound healing and transwell migration assays. MTT and LDH release assays were used to analyze cell growth and cytotoxicity. Flow cytometry was employed to detect cell surface markers of cancer stem cell population. Expression and activity of matrix metalloproteinases were probed with qRT-PCR and zymogen assay. To identify pathways affected by sublethal dose of Dox, exploratory RNAseq was performed and results were verified by qRT-PCR in multiple cell lines (MCF7, ZR75-1 and U-2OS). Regulation of Src Family kinases (SFK) by key players in DNA damage response was assessed by siRNA knockdown along with western blot and qRT-PCR. Dasatinib and siRNA for Fyn and Yes was employed to inhibit SFKs and verify their role in increased migration and invasion in MCF7 cells treated with sublethal doses of Dox.
resultsThe results show that sublethal Dox treatment leads to increased migration and invasion in otherwise non-invasive MCF7 breast cancer cells. Mechanistically, these effects were independent of the epithelial mesenchymal transition, were not due to increased cancer stem cell population, and were not observed with other chemotherapies. Instead, sublethal Dox induces expression of multiple SFK-including Fyn, Yes, and Src-partly in a p53 and ATR-dependent manner. These effects were validated in multiple cell lines. Functionally, inhibiting SFKs with Dasatinib and specific downregulation of Fyn suppressed Dox-induced migration and invasion of MCF7 cells.
conclusionsOverall, this study demonstrates that sublethal doses of Dox activate a pro-invasive, pro-migration program in cancer cells. Furthermore, by identifying SFKs as key mediators of these effects, our results define a potential therapeutic strategy to mitigate local invasion through co-treatment with Dasatinib.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.