ArticleOncogene2016
Non-migratory tumorigenic intrinsic cancer stem cells ensure breast cancer metastasis by generation of CXCR4(+) migrating cancer stem cells.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 60 citations in OpenAlex.
- Nestin and SOX2 Maintain self-renewal Abilities of Different Pancreatic Cancer Stem Cell Populations.Stem cell reviews and reports · 2026Article
- hsa-miR-5688 inhibits FOXC1-OCT4/SOX2 feedforward loop that drives chemoresistance in breast cancer stem cells.Molecular therapy. Oncology · 2025Article
- In-silico analysis unveiling the role of cancer stem cells in immunotherapy resistance of immune checkpoint-high pancreatic adenocarcinoma.Scientific reports · 2025Article
- Review
- Article
- Breast cancer stem cells generate immune-suppressive T regulatory cells by secreting TGFβ to evade immune-elimination.Discover oncology · 2023Article
- Microbiota-Derived Natural Products Targeting Cancer Stem Cells: Inside the Gut Pharma Factory.International journal of molecular sciences · 2023Review
- Tumor-associated macrophages: an effective player of the tumor microenvironment.Frontiers in immunology · 2023Review
- Tumour Stem Cells in Breast Cancer.International journal of molecular sciences · 2022Review
- ENTREP/FAM189A2 encodes a new ITCH ubiquitin ligase activator that is downregulated in breast cancer.EMBO reports · 2022Article
- Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment.Cancers · 2021Review
- Evaluation of breast cancer stem cells in human primary breast carcinoma and their role in aggressive behavior of the disease.Journal of clinical and translational research · 2021Article
- A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner.Angiogenesis · 2021Article
- Suppression of poised oncogenes by ZMYND8 promotes chemo-sensitization.Cell death & disease · 2020Article
- The Breast Cancer Stem Cells Traits and Drug Resistance.Frontiers in pharmacology · 2020Review
- A novel role of tumor suppressor ZMYND8 in inducing differentiation of breast cancer cells through its dual-histone binding function.Journal of biosciences · 2020Article
- Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration.Scientific reports · 2019Article
- MiR-873/PD-L1 axis regulates the stemness of breast cancer cells.EBioMedicine · 2019Article
- Metformin attenuates cells stemness and epithelial‑mesenchymal transition in colorectal cancer cells by inhibiting the Wnt3a/β‑catenin pathway.Molecular medicine reports · 2019Article
- Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the role of metastatic cancer stem cells (mCSCs) in tumor progression has been well documented, our study reveals a hitherto unidentified role of tumorigenic intrinsic CSCs (iCSCs) in breast cancer metastasis. We show that unlike highly migratory mCSCs residing in the breast tumor disseminating/peripheral regions, iCSCs populate the inner mass of the tumor and are non-migratory. However iCSCs, via paracrine signaling, induce conversion of non-stem cancer cells to CSCs that (i) are identical to the previously reported mCSCs, and (ii) in contrast to iCSCs, express chemokine receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), which is crucial for their metastatic potential. These mCSCs also demonstrate high in vivo tumorigenicity. Physical non-participation of iCSCs in metastasis is further validated in vivo, where only mCSCs are found to exist in the metastatic sites, lymph nodes and bone marrow, whereas the primary tumor retains both iCSCs and mCSCs. However, iCSCs ensure metastasis since their presence is crucial for deliverance of highly metastatic CXCR4(+) mCSCs to the migrating fraction of cells. Cumulatively, these results unveil a novel role of iCSCs in breast cancer metastasis as parental regulators of CXCR4(+) mCSCs, and highlight the therapeutic requisite of targeting iCSCs, but not CXCR4(+) mCSCs, to restrain breast cancer metastasis from the root by inhibiting the generation of mCSCs from iCSCs. Considering the pivotal role of iCSCs in tumor metastasis, the possibility of metastasis to be a 'stem cell phenomena' is suggested.
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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.