ArticleScience signaling2017
Differential abundance of CK1α provides selectivity for pharmacological CK1α activators to target WNT-dependent tumors.
Article in Science signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- CK1α agonists attenuate medulloblastoma stemness and relapse risk.Cell death & disease · 2026Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- RBM15-MKL1 fusion protein promotes leukemia via m6A methylation and Wnt pathway activation.Blood · 2025Article
- The TRIP12 E3 ligase induces SWI/SNF component BRG1-β-catenin interaction to promote Wnt signaling.Nature communications · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Wnt signaling inhibits casein kinase 1α activity by modulating its interaction with protein phosphatase 2A.Cell reports · 2025Article
- Exploring the role of casein kinase 1α splice variants across cancer cell lines.Biochemical and biophysical research communications · 2024Article
- Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review).Oncology reports · 2024Review
- Mechanistic insights into medulloblastoma relapse.Pharmacology & therapeutics · 2024Review
- Casein Kinase 1α-A Target for Prostate Cancer Therapy?Cancers · 2024Review
- Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy.Journal of hematology & oncology · 2024Review
- Article
- Targeting Stem Cells and Dysplastic Features With Dual MEK/ERK and STAT3 Suppression in Gastric Carcinogenesis.Gastroenterology · 2024Article
- The USP46 complex deubiquitylates LRP6 to promote Wnt/β-catenin signaling.Nature communications · 2023Article
- A New Wave of Targeting 'Undruggable' Wnt Signaling for Cancer Therapy: Challenges and Opportunities.Cells · 2023Review
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
- Response to BRAF-targeted Therapy Is Enhanced by Cotargeting VEGFRs or WNT/β-Catenin Signaling in BRAF-mutant Colorectal Cancer Models.Molecular cancer therapeutics · 2022Article
- Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.Molecular cancer · 2022Review
- Breast cancer: molecular mechanisms of underlying resistance and therapeutic approaches.American journal of cancer research · 2022Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 1 country.
Funding
Abstract
Constitutive WNT activity drives the growth of various human tumors, including nearly all colorectal cancers (CRCs). Despite this prominence in cancer, no WNT inhibitor is currently approved for use in the clinic largely due to the small number of druggable signaling components in the WNT pathway and the substantial toxicity to normal gastrointestinal tissue. We have shown that pyrvinium, which activates casein kinase 1α (CK1α), is a potent inhibitor of WNT signaling. However, its poor bioavailability limited the ability to test this first-in-class WNT inhibitor in vivo. We characterized a novel small-molecule CK1α activator called SSTC3, which has better pharmacokinetic properties than pyrvinium, and found that it inhibited the growth of CRC xenografts in mice. SSTC3 also attenuated the growth of a patient-derived metastatic CRC xenograft, for which few therapies exist. SSTC3 exhibited minimal gastrointestinal toxicity compared to other classes of WNT inhibitors. Consistent with this observation, we showed that the abundance of the SSTC3 target, CK1α, was decreased in WNT-driven tumors relative to normal gastrointestinal tissue, and knocking down CK1α increased cellular sensitivity to SSTC3. Thus, we propose that distinct CK1α abundance provides an enhanced therapeutic index for pharmacological CK1α activators to target WNT-driven tumors.
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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.