ArticleJournal of experimental & clinical cancer research : CR2020
A pre-existing population of ZEB2
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 82 citations in OpenAlex.
- Cancer Stem Cell Quiescence: Molecular and Microenvironmental Evidence for an Actively Regulated Adaptive Survival Strategy.Cancer medicine · 2026Review
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
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- Ubiquitination of DDX21 by HERC2 induces a dormancy-like phenotype via the NUCKS1-p21/p27 axis to promote radio-resistance in colorectal cancer cells.Cell death & disease · 2026Article
- Article
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Breaking the Resistance: Photodynamic Therapy in Cancer Stem Cell-Driven Tumorigenesis.Pharmaceutics · 2025Review
- Cancer stem cells and niches: challenges in immunotherapy resistance.Molecular cancer · 2025Review
- Aging directs the differential evolution of KRAS-driven lung adenocarcinoma.bioRxiv : the preprint server for biology · 2025Article
- Multi-omics dissection of tumor microenvironment-mediated drug resistance: mechanisms and therapeutic reprogramming.Frontiers in pharmacology · 2025Review
- CDH1-involved Ubiquitination of SIRT5 Promotes the Entry of Colorectal Cancer Cells into Quiescence and Enhances Cell Stemness.Anti-cancer agents in medicinal chemistry · 2025Article
- ZEB2 upregulation modulates the polarization of TAMs toward the immunosuppressive state in EGFR-TKI-resistant NSCLC.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Mechanisms of HIF1A-mediated immune evasion in gastric cancer and the impact on therapy resistance.Cell biology and toxicology · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Targeting EMT using low-dose Teniposide by downregulating ZEB2-driven activation of RNA polymerase I in breast cancer.Cell death & disease · 2024Article
- CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Dormancy and awakening of cancer cells: the extracellular vesicle-mediated cross-talk between Dr. Jekill and Mr. Hyde.Frontiers in immunology · 2024Review
- How circulating tumor cluster biology contributes to the metastatic cascade: from invasion to dissemination and dormancy.Cancer metastasis reviews · 2023Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundQuiescent/slow cycling cells have been identified in several tumors and correlated with therapy resistance. However, the features of chemoresistant populations and the molecular factors linking quiescence to chemoresistance are largely unknown.
methodsA population of chemoresistant quiescent/slow cycling cells was isolated through PKH26 staining (which allows to separate cells on the basis of their proliferation rate) from colorectal cancer (CRC) xenografts and subjected to global gene expression and pathway activation analyses. Factors expressed by the quiescent/slow cycling population were analyzed through lentiviral overexpression approaches for their ability to induce a dormant chemoresistant state both in vitro and in mouse xenografts. The correlation between quiescence-associated factors, CRC consensus molecular subtype and cancer prognosis was analyzed in large patient datasets.
resultsUntreated colorectal tumors contain a population of quiescent/slow cycling cells with stem cell features (quiescent cancer stem cells, QCSCs) characterized by a predetermined mesenchymal-like chemoresistant phenotype. QCSCs expressed increased levels of ZEB2, a transcription factor involved in stem cell plasticity and epithelial-mesenchymal transition (EMT), and of antiapototic factors pCRAF and pASK1. ZEB2 overexpression upregulated pCRAF/pASK1 levels resulting in increased chemoresistance, enrichment of cells with stemness/EMT traits and proliferative slowdown of tumor xenografts. In parallel, chemotherapy treatment of tumor xenografts induced the prevalence of QCSCs with a stemness/EMT phenotype and activation of the ZEB2/pCRAF/pASK1 axis, resulting in a chemotherapy-unresponsive state. In CRC patients, increased ZEB2 levels correlated with worse relapse-free survival and were strongly associated to the consensus molecular subtype 4 (CMS4) characterized by dismal prognosis, decreased proliferative rates and upregulation of EMT genes.
conclusionsThese results show that chemotherapy-naive tumors contain a cell population characterized by a coordinated program of chemoresistance, quiescence, stemness and EMT. Such population becomes prevalent upon drug treatment and is responsible for chemotherapy resistance, thus representing a key target for more effective therapeutic approaches.
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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.