ArticleCancer research2022
Autocrine Canonical Wnt Signaling Primes Noncanonical Signaling through ROR1 in Metastatic Castration-Resistant Prostate Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 36 citations in OpenAlex.
- ADT and activation of HGF and WNT axes in double-null prostate cancer.Nature reviews. Urology · 2026Review
- Canonical Wnt signaling in the regulation of prostate cancer stem cells: a key driver of castration-resistant prostate cancer and a therapeutic opportunity.Journal of translational medicine · 2026Review
- APOE ε2/ε3 is associated with multi-layered protection against prostate cancer in Chinese men.World journal of urology · 2026Article
- Wnt signaling and the tumor microenvironment: implications for cancer progression and therapeutics.Oncogene · 2026Review
- Wntless degradation mediated by CaMKII inhibition drives endoplasmic reticulum stress and apoptosis.Cell reports · 2026Article
- Cell surface oncofetal antigens in prostate cancer: therapeutic potential and radioligand targeting.EJNMMI research · 2026Review
- Signalling pathways in a nutshell: from pathogenesis to therapeutical implications in prostate cancer.Annals of medicine · 2025Review
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Targeting the tumour cell surface in advanced prostate cancer.Nature reviews. Urology · 2025Review
- The Role of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) in Cancer Stem Cell Signaling.International journal of molecular sciences · 2025Review
- SOX2 utilizes FOXA1 as a heteromeric transcriptional partner to drive proliferation in therapy-resistant prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Deciphering the Tumor Microenvironment in Prostate Cancer: A Focus on the Stromal Component.Cancers · 2024Review
- Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.Molecular cancer · 2024Review
- Characterization of Wnt Signaling Pathway Aberrations in Metastatic Prostate Cancer.Molecular cancer research : MCR · 2024Article
- Prostate cancer-induced endothelial-cell-to-osteoblast transition drives immunosuppression in the bone-tumor microenvironment through Wnt pathway-induced M2 macrophage polarization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration.Journal of neuroinflammation · 2024Article
- Prostate cancer genetic background. The introduction of genetic testing in the determination of high-risk prostate cancer cases and selection of targeted chemotherapy in advanced prostate cancer patients.Central European journal of urology · 2024Review
- The PENGUIN approach to reconstruct protein interactions at enhancer-promoter regions and its application to prostate cancer.Nature communications · 2023Article
- Brief Report: circRUNX1 as Potential Biomarker for Cancer Recurrence in EGFR Mutation-Positive Surgically Resected NSCLC.JTO clinical and research reports · 2023Article
- Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.Current pharmacology reports · 2023Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Wnt signaling driven by genomic alterations in genes including APC and CTNNB, which encodes β-catenin, have been implicated in prostate cancer development and progression to metastatic castration-resistant prostate cancer (mCRPC). However, nongenomic drivers and downstream effectors of Wnt signaling in prostate cancer and the therapeutic potential of targeting this pathway in prostate cancer have not been fully established. Here we analyzed Wnt/β-catenin signaling in prostate cancer and identified effectors distinct from those found in other tissues, including aryl hydrocarbon receptor and RUNX1, which are linked to stem cell maintenance, and ROR1, a noncanonical Wnt5a coreceptor. Wnt/β-catenin signaling-mediated increases in ROR1 enhanced noncanonical responses to Wnt5a. Regarding upstream drivers, APC genomic loss, but not its epigenetic downregulation commonly observed in prostate cancer, was strongly associated with Wnt/β-catenin pathway activation in clinical samples. Tumor cell upregulation of the Wnt transporter Wntless (WLS) was strongly associated with Wnt/β-catenin pathway activity in primary prostate cancer but also associated with both canonical and noncanonical Wnt signaling in mCRPC. IHC confirmed tumor cell WLS expression in primary prostate cancer and mCRPC, and patient-derived prostate cancer xenografts expressing WLS were responsive to treatment with Wnt synthesis inhibitor ETC-1922159. These findings reveal that Wnt/β-catenin signaling in prostate cancer drives stem cell maintenance and invasion and primes for noncanonical Wnt signaling through ROR1. They further show that autocrine Wnt production is a nongenomic driver of canonical and noncanonical Wnt signaling in prostate cancer, which can be targeted with Wnt synthesis inhibitors to suppress tumor growth. SIGNIFICANCE: This work provides fundamental insights into Wnt signaling and prostate cancer cell biology and indicates that a subset of prostate cancer driven by autocrine Wnt signaling is sensitive to Wnt synthesis inhibitors.
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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.