ArticleProceedings of the National Academy of Sciences of the United States of America2011
Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 119 citations in OpenAlex.
- Tumor-Associated Macrophages as Therapeutic Targets: Deciphering Interaction Networks and Advancing Clinical Translation.MedComm · 2026Review
- Review
- Acidosis attenuates the hypoxic stabilization of HIF-1α by activating lysosomal degradation.The Journal of cell biology · 2025Article
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- Goblet cell differentiation subgroups in colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting.Genes & diseases · 2024Review
- Phenotypic screen of sixty-eight colorectal cancer cell lines identifies CEACAM6 and CEACAM5 as markers of acid resistance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TMT-based quantitative proteomic analysis of spheroid cells of endometrial cancer possessing cancer stem cell properties.Stem cell research & therapy · 2023Article
- Advances and Challenges in Cancer Stem Cells for Onco-Therapeutics.Stem cells international · 2023Review
- Tumor-associated macrophages: an effective player of the tumor microenvironment.Frontiers in immunology · 2023Review
- Hypoxia effects on cancer stem cell phenotype in colorectal cancer: a mini-review.Molecular biology reports · 2021Review
- Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway.Autophagy · 2020Article
- Radiotherapy targeting cancer stem cells "awakens" them to induce tumour relapse and metastasis in oral cancer.International journal of oral science · 2020Review
- Fibroblast-Derived Extracellular Vesicles Induce Colorectal Cancer Progression by Transmitting Amphiregulin.Frontiers in cell and developmental biology · 2020Article
- The Relevance of Transcription Factors in Gastric and Colorectal Cancer Stem Cells Identification and Eradication.Frontiers in cell and developmental biology · 2020Review
- Review
- Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma.Clinical and translational medicine · 2019Review
- Review
- Hypoxia potentiates gemcitabine-induced stemness in pancreatic cancer cells through AKT/Notch1 signaling.Journal of experimental & clinical cancer research : CR · 2018Article
- Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity.International journal of molecular sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia is an important regulator of normal and cancer stem cell (CSC) differentiation. Colorectal CSCs from SW1222, LS180, and CCK81 colorectal cancer-derived cell lines are able to differentiate into complex 3D lumen-containing structures in normoxia, whereas in hypoxia, they form undifferentiated dense colonies that have reduced expression of the enterocyte differentiation marker CDX1, lack goblet cell formation, and have increased expression of BMI1 and activated Notch1. Hypoxia increases the clonogenicity of CSCs, which is cumulative as each round of hypoxia enriches for more CSCs. The hypoxic phenotype is reversible, because cells from hypoxic-dense colonies are able to reform differentiated structures when regrown in normoxia. We show that CDX1 is able to stimulate the generation of lumens even in hypoxia and has a negative feedback on BMI1 expression. Knockdown of CDX1 reduces lumen formation but does not affect goblet cell formation, suggesting that enterocytes and goblet cells form from different progenitor cells. Notch inhibition by dibenzazepine (DBZ) allowed CSCs to form goblet cells in both normoxia and hypoxia. Finally, we show that Hif1α, but not CA9, is an important mediator of the effects of hypoxia on the clonogenicity and differentiation of CSCs. In summary, hypoxia maintains the stem-like phenotype of colorectal cell line-derived CSCs and prevents differentiation of enterocytes and goblet cells by regulating CDX1 and Notch1, suggesting that this regulation is an important component of how hypoxia controls the switch between stemness and differentiation in CSCs.
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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.