ArticleMolecular cancer2010
Smoothened as a new therapeutic target for human osteosarcoma.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 106 citations in OpenAlex.
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- Review
- Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application.Journal of cancer research and clinical oncology · 2023Review
- Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype.Oncogene · 2023Article
- Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.International journal of molecular sciences · 2023Review
- Article
- Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers.International journal of molecular sciences · 2023Review
- STAT3 is required for Smo-dependent signaling and mediates Smo-targeted treatment resistance and tumorigenesis in Shh medulloblastoma.Molecular oncology · 2022Article
- Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome.Bioengineered · 2021Article
- Excellent Early Outcomes of Combined Chemotherapy With Arsenic Trioxide for Stage 4/M Neuroblastoma in Children: A Multicenter Nonrandomized Controlled Trial.Oncology research · 2021Article
- Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies.Cancers · 2021Review
- The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury.Journal of orthopaedic surgery and research · 2021Article
- Article
- Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy.International journal of molecular sciences · 2020Review
- Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies.Cells · 2020Review
- Review
- Review
- Evaluation of canonical Hedgehog signaling pathway inhibition in canine osteosarcoma.PloS one · 2020Article
- Melarsomine suppresses canine osteosarcoma cell survival via inhibition of Hedgehog-GLI signaling.The Journal of veterinary medical science · 2019Article
- Effect of RAB31 silencing on osteosarcoma cell proliferation and migration through the Hedgehog signaling pathway.Journal of bone and mineral metabolism · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Hedgehog signaling pathway functions as an organizer in embryonic development. Recent studies have demonstrated constitutive activation of Hedgehog pathway in various types of malignancies. However, it remains unclear how Hedgehog pathway is involved in the pathogenesis of osteosarcoma. To explore the involvement of aberrant Hedgehog pathway in the pathogenesis of osteosarcoma, we investigated the expression and activation of Hedgehog pathway in osteosarcoma and examined the effect of SMOOTHENED (SMO) inhibition.
resultsTo evaluate the expression of genes of Hedgehog pathway, we performed real-time PCR and immunohistochemistry using osteosarcoma cell lines and osteosarcoma biopsy specimens. To evaluate the effect of SMO inhibition, we did cell viability, colony formation, cell cycle in vitro and xenograft model in vivo. Real-time PCR revealed that osteosarcoma cell lines over-expressed Sonic hedgehog, Indian hedgehog, PTCH1, SMO, and GLI. Real-time PCR revealed over-expression of SMO, PTCH1, and GLI2 in osteosarcoma biopsy specimens. These findings showed that Hedgehog pathway is activated in osteosarcomas. Inhibition of SMO by cyclopamine, a specific inhibitor of SMO, slowed the growth of osteosarcoma in vitro. Cell cycle analysis revealed that cyclopamine promoted G1 arrest. Cyclopamine reduced the expression of accelerators of the cell cycle including cyclin D1, cyclin E1, SKP2, and pRb. On the other hand, p21(cip1) wprotein was up-regulated by cyclopamine treatment. In addition, knockdown of SMO by SMO shRNA prevents osteosarcoma growth in vitro and in vivo.
conclusionsThese findings suggest that inactivation of SMO may be a useful approach to the treatment of patients with osteosarcoma.
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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.