ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 1 of them a synthesis that pooled it.
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Who cites it
194 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Prognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta-Analysis.PloS one · 2015Pooled it
- A phase 2 study of dasatinib in recurrent clear cell carcinoma of the ovary, fallopian tube, peritoneum or endometrium: NRG oncology/gynecologic oncology group study 0283.Gynecologic oncology · 2023Trial
- Review
- IL-24 Induces Cell Dormancy and Oxaliplatin Resistance in Colon Cancer Cells by Activating NF-κB Pathway.Molecular carcinogenesis · 2026Article
- GDF15 promotes 5-Fluorouracil and Oxaliplatin resistance by promoting stem cell-like phenotype in colorectal cancer.British journal of cancer · 2026Article
- Factors Associated with the Timing of Liver Metastasis After Colorectal Cancer Surgery: A Retrospective Multicenter Study.Cancers · 2026Article
- Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.Molecular oncology · 2026Review
- Article
- Targeting TYRO3 attenuates apoptotic cell-driven cancer stemness in triple negative breast cancer.Cell communication and signaling : CCS · 2026Article
- Regulating the dormancy of cancer stem cells: a novel approach to preventing cancer relapse.Cell death & disease · 2026Review
- Dormancy in Metastatic Colorectal Cancer: Tissue Engineering Opportunities forTissue engineering. Part B, Reviews · 2026Review
- MAVS as a Key Regulator of Tumor Proliferation, Survival, the Tumor Microenvironment, and Immunity.Biomolecules · 2026Article
- Decellularized Extracellular Matrix Scaffolds to Engineer the Dormant Landscape of Microscopic Colorectal Cancer Liver Metastasis.Advanced healthcare materials · 2026Article
- Plexin A2 Knockdown Enhances Apoptosis in Chemotherapy Treated Melanoma Cells.Oncology research · 2026Article
- Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models.Nature communications · 2025Article
- Monod: model-based discovery and integration through fitting stochastic transcriptional dynamics to single-cell sequencing data.Nature methods · 2025Article
- Combination Treatment of Carboxyl Esterase 2-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhances the Inhibition of Tumor Growth by Irinotecan in PC3, a Castration-Resistant Prostate Cancer Model.Current issues in molecular biology · 2025Article
- Overcoming colorectal cancer and cancer stem cell resistance with photodynamic therapy: new frontiers in oncology.RSC advances · 2025Review
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Review
134 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors.
Funding
Abstract
purposeMetastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery.
resultsWe show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell-like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively).
conclusionsWe identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer.
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