ArticleOncogene2014
Mitochondrial retrograde signaling induces epithelial-mesenchymal transition and generates breast cancer stem cells.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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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.
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Who cites it
95 citing papers in PubMed, 155 citations in OpenAlex.
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- Ophiobolin A impacts mitochondrial redox biology in an epithelial-mesenchymal transition (EMT)-specific manner.Cancer cell international · 2026Article
- Cancer as an evolutionary reversal-time for a paradigm shift.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Article
- Navigating the Metabolic-Genomic Paradigm: Mitochondrial Reprogramming as a Driver of Cancer Plasticity.Oncology research · 2026Review
- The Emerging Role of Mitochondrial Dysfunction in Thyroid Cancer: Mediating Tumor Progression, Drug Resistance, and Reshaping of the Immune Microenvironment.Biomolecules · 2025Review
- PPARδ Orchestrates a Prometastatic Metabolic Response to Microenvironmental Cues in Pancreatic Cancer.Cancer research · 2025Article
- Combination strategies of gut microbiota in cancer therapy through metabolic reprogramming and immune remodeling.Cell communication and signaling : CCS · 2025Review
- The movement of mitochondria in breast cancer: internal motility and intercellular transfer of mitochondria.Clinical & experimental metastasis · 2024Review
- Beyond Death: Unmasking the Intricacies of Apoptosis Escape.Molecular diagnosis & therapy · 2024Review
- Mitochondria transcription and cancer.Cell death discovery · 2024Review
- Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue.Cells · 2024Article
- PRRG4 regulates mitochondrial function and promotes migratory behaviors of breast cancer cells through the Src-STAT3-POLG axis.Cancer cell international · 2023Article
- Correction to: YY1 inactivated transcription co-regulator PGC-1α to promote mitochondrial dysfunction of early diabetic nephropathy-associated tubulointerstitial fibrosis.Cell biology and toxicology · 2023Article
- Oxidative stress regulation and related metabolic pathways in epithelial-mesenchymal transition of breast cancer stem cells.Stem cell research & therapy · 2023Review
- ZNF281 inhibits mitochondrial biogenesis to facilitate metastasis of hepatocellular carcinoma.Cell death discovery · 2023Article
- Adipose Mesenchymal Stem Cell-Derived Exosomes Promote the Regeneration of Corneal Endothelium Through Ameliorating Senescence.Investigative ophthalmology & visual science · 2023Article
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- Role of mitochondrial alterations in human cancer progression and cancer immunity.Journal of biomedical science · 2023Review
- The role of tumor microenvironment on cancer stem cell fate in solid tumors.Cell communication and signaling : CCS · 2023Review
- YY1 inactivated transcription co-regulator PGC-1α to promote mitochondrial dysfunction of early diabetic nephropathy-associated tubulointerstitial fibrosis.Cell biology and toxicology · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Metastatic breast tumors undergo epithelial-to-mesenchymal transition (EMT), which renders them resistant to therapies targeted to the primary cancers. The mechanistic link between mtDNA (mitochondrial DNA) reduction, often seen in breast cancer patients, and EMT is unknown. We demonstrate that reducing mtDNA content in human mammary epithelial cells (hMECs) activates Calcineurin (Cn)-dependent mitochondrial retrograde signaling pathway, which induces EMT-like reprogramming to fibroblastic morphology, loss of cell polarity, contact inhibition and acquired migratory and invasive phenotype. Notably, mtDNA reduction generates breast cancer stem cells. In addition to retrograde signaling markers, there is an induction of mesenchymal genes but loss of epithelial markers in these cells. The changes are reversed by either restoring the mtDNA content or knockdown of CnAα mRNA, indicating the causal role of retrograde signaling in EMT. Our results point to a new therapeutic strategy for metastatic breast cancers targeted to the mitochondrial retrograde signaling pathway for abrogating EMT and attenuating cancer stem cells, which evade conventional therapies. We report a novel regulatory mechanism by which low mtDNA content generates EMT and cancer stem cells in hMECs.
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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 OpenQuestion graph.