ArticleMolecular cancer2004
Activation of the hedgehog pathway in advanced prostate cancer.
Article in Molecular cancer, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed.
- Recurrent mechanisms of biallelic epigenetic inactivation reveal new putative tumour suppressor genes in prostate cancer.Nature communications · 2026Article
- From fungus fighter to cancer slayer: itraconazole as a multifaceted candidate for drug-resistant prostate cancer.Prostate cancer and prostatic diseases · 2026Review
- Multifaceted role of primary cilia and ciliary proteins: A potential nexus for hedgehog signaling and prostate cancer.Biochimica et biophysica acta. Molecular basis of disease · 2026Review
- Signalling pathways in a nutshell: from pathogenesis to therapeutical implications in prostate cancer.Annals of medicine · 2025Review
- Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.Oncogene · 2025Article
- A real-world experience of pembrolizumab monotherapy in microsatellite instability-high and/or tumor mutation burden-high metastatic castration-resistant prostate cancer: outcome analysis.Prostate cancer and prostatic diseases · 2025Article
- PlexinD1 is a driver and a therapeutic target in advanced prostate cancer.EMBO molecular medicine · 2025Article
- Review
- The Role of Mutated Calreticulin in the Pathogenesis ofInternational journal of molecular sciences · 2024Article
- Effects of Isoxazolyl Steroids on Key Genes of Sonic Hedgehog Cascade Expression in Tumor Cells.Molecules (Basel, Switzerland) · 2024Article
- High NaCl Concentrations in Water Are Associated with Developmental Abnormalities and Altered Gene Expression in Zebrafish.International journal of molecular sciences · 2024Article
- Rapid induction of dopaminergic neuron-like cells from human fibroblasts by autophagy activation with only 2-small molecules.3 Biotech · 2024Article
- CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/β-catenin signaling pathways in clear cell renal cell carcinoma.Cancer cell international · 2023Article
- Microbiome and MicroRNA or Long Non-Coding RNA-Two Modern Approaches to Understanding Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2023Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Inhibition of the transcription factor ZNF281 by SUFU to suppress tumor cell migration.Cell death and differentiation · 2023Article
- Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (Biomedicines · 2023Article
- The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update.Frontiers in immunology · 2023Review
- The emerging roles of Hedgehog signaling in tumor immune microenvironment.Frontiers in oncology · 2023Review
100 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
backgroundThe hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications.
resultsHere we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP), are detected in over 70% of prostate tumors with Gleason scores 8-10, but in only 22% of tumors with Gleason scores 3-6. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. To identify the mechanism of the hedgehog signaling activation, we examine expression of Su(Fu) protein, a negative regulator of the hedgehog pathway. We find that Su(Fu) protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu). Furthermore, expression of sonic hedgehog protein is detected in majority of PTCH1 positive tumors (24 out of 27). High levels of hedgehog target genes are also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3). We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells.
conclusionOur data indicate that activation of the hedgehog pathway, through loss of Su(Fu) or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have significant implications of prostate cancer therapeutics.
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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.