ArticleProceedings of the National Academy of Sciences of the United States of America2016
Axitinib blocks Wnt/β-catenin signaling and directs asymmetric cell division in cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- Pooled it
- Competitive Binding of UBA52 and HOPX Modulates β-catenin Stability in Colorectal Cancer in the Context of High-Iron Intake.International journal of biological sciences · 2026Article
- Targeting asymmetric division in cancer stem cells: implications for relapse and resistance.Cancer cell international · 2025Review
- GSK3β Regulates a Novel β-Catenin Degradation Pathway via the GID Complex in Wnt Signaling.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- Suppressing protein damage response to overcome multidrug resistance in cancer therapy.Cell discovery · 2025Article
- A working group report from the 2024 National Cancer Institute / Gynecologic Cancer Steering Committee endometrial cancer clinical trials planning meeting: refining the approach to endometrial cancer in the immunotherapy era.Journal of the National Cancer Institute · 2025Article
- Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity.Nature chemistry · 2025Article
- SYS-1/beta-catenin inheritance and regulation by Wnt signaling during asymmetric cell division.Molecular biology of the cell · 2025Article
- Non-kinase off-target inhibitory activities of clinically-relevant kinase inhibitors.European journal of medicinal chemistry · 2024Review
- Integrative genomics identifies SHPRH as a tumor suppressor gene in lung adenocarcinoma that regulates DNA damage response.British journal of cancer · 2024Article
- Chemoproteomics, A Broad Avenue to Target Deconvolution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- β-catenin inhibitors in cancer therapeutics: intricacies and way forward.Bioengineered · 2023Review
- Small molecule activates citrullination through targeting PAD2.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Target identification of small molecules: an overview of the current applications in drug discovery.BMC biotechnology · 2023Review
- Enhancement of TKI sensitivity in lung adenocarcinoma through m6A-dependent translational repression of Wnt signaling by circ-FBXW7.Molecular cancer · 2023Article
- Targeting the PTP1B-Bcr-Abl1 interaction for the degradation of T315I mutant Bcr-Abl1 in chronic myeloid leukemia.Cancer science · 2023Article
- Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.Frontiers in pharmacology · 2023Article
- What we have learnt fromHeliyon · 2022Review
- β-catenin links cell seeding density to global gene expression during mouse embryonic stem cell differentiation.iScience · 2022Article
- An update of label-free protein target identification methods for natural active products.Theranostics · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic mutations of the Wnt (wingless)/β-catenin pathway are frequently observed in major cancer types. Thus far, however, no therapeutic agent targeting Wnt/β-catenin signaling is available for clinical use. Here we demonstrate that axitinib, a clinically approved drug, strikingly blocks Wnt/β-catenin signaling in cancer cells, zebrafish, and Apc(min/+) mice. Notably, axitinib dramatically induces Wnt asymmetry and nonrandom DNA segregation in cancer cells by promoting nuclear β-catenin degradation independent of the GSK3β (glycogen synthase kinase3β)/APC (adenomatous polyposis coli) complex. Using a DARTS (drug affinity-responsive target stability) assay coupled to 2D-DIGE (2D difference in gel electrophoresis) and mass spectrometry, we have identified the E3 ubiquitin ligase SHPRH (SNF2, histone-linker, PHD and RING finger domain-containing helicase) as the direct target of axitinib in blocking Wnt/β-catenin signaling. Treatment with axitinib stabilizes SHPRH and thereby increases the ubiquitination and degradation of β-catenin. Our findings suggest a previously unreported mechanism of nuclear β-catenin regulation and indicate that axitinib, a clinically approved drug, would provide therapeutic benefits for cancer patients with aberrant nuclear β-catenin activation.
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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.