ArticleNature cell biology2020
Overcoming Wnt-β-catenin dependent anticancer therapy resistance in leukaemia stem cells.
Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
82 citing papers in PubMed, 134 citations in OpenAlex.
- Colorectal cancer molecular subtypes and prognostic models based on NET-related genes and oxidative stress-associated signaling.Medicine · 2026Article
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- TOE1 is a β-catenin interacting protein regulating the proliferation of hematopoietic cells through PAK2 modulation.Stem cell reports · 2026Article
- Silencing CD24 Inhibits Proliferation, Migration, and Chemoresistance in Triple-Negative Breast Cancer Cells.Pharmaceutical research · 2026Article
- Macrophage-delivered Nifuroxazide reprograms immunosuppressive microenvironment and synergizes with oxaliplatin for enhanced anti-hepatocellular carcinoma therapy.Journal of nanobiotechnology · 2026Article
- Regulating Ferroptosis in Leukemic Stem Cells: From Stemness Preservation to Targeted Differentiation Strategies.Stem cell reviews and reports · 2026Review
- DHDK, a Plant-Derived Natural Small Molecule, Protects Against Doxorubicin-Induced Cardiotoxicity via the PPARG-CPT1B-FAO Axis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- TAM family kinases are potential candidate targets for therapeutic intervention in chronic myeloid leukemia.Discover oncology · 2025Article
- Overcoming resistance to anti-PD-L1 immunotherapy: mechanisms, combination strategies, and future directions.Molecular cancer · 2025Review
- Targeting macrophages in cancer immunotherapy: Frontiers and challenges.Journal of advanced research · 2025Review
- β-Catenin interacts with canonical RBPs including MSI2 to associate with a Wnt signalling mRNA network in myeloid leukaemia cells.Oncogene · 2025Article
- Cancer network pharmacology: multi-network regulatory mechanisms and future directions.Medical oncology (Northwood, London, England) · 2025Review
- Targeting LMO2-induced autocrine FLT3 signaling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia.Leukemia · 2025Article
- Comparative assessment of antitumor effects between doxorubicin and mitochondria-targeted doxorubicin in combination with radiotherapy.Oncology research · 2025Article
- Decoding CD24: Roles of chemoradiotherapy resistance and potential as therapeutic targets.Oncology research · 2025Review
- Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Stemness in solid malignancies: coping with immune attack.Nature reviews. Cancer · 2025Review
- Review
- Characterization of stem cell landscape and assessing the stemness degree to aid clinical therapeutics in hematologic malignancies.Scientific reports · 2024Article
- Intestinal stem cells in intestinal homeostasis and colorectal tumorigenesis.Life medicine · 2024Review
22 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
36 authors at 10 institutions in 2 countries.
Funding
Abstract
Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-β-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.
Indexed as
Identifiers
What OpenQuestion holds
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.