ArticleOncotarget2016
In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 111 citations in OpenAlex.
- Vismodegib Exerts a Pleotropic Effect on Topotecan-Resistant and Sensitive Ovarian Cancer Cell Lines in 2D and 3D Cell Culture Models.Molecules (Basel, Switzerland) · 2026Article
- Ldha Regulates Osteosarcoma Lung Metastasis through Hedgehog Signaling.Cancer research communications · 2026Article
- Increased expression of PTCH1 and GLI1 in Bangladeshi TNBC Patients after Treatment with Doxorubicin and Cyclophosphamide Suggests a Favorable Response to Chemotherapy.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- GPR137-RAB8A activation promotes ovarian cancer development via the Hedgehog pathway.Journal of experimental & clinical cancer research : CR · 2025Article
- Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Breast Cancer Stem Cells and Tumor Heterogeneity: Characteristics and Therapeutic Strategies.Cancers · 2024Review
- Identification of Novel GANT61 Analogs with Activity in Hedgehog Functional Assays and GLI1-Dependent Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy.Cells · 2024Review
- Computational investigation of naturally occurring anticancer agents in regulating Hedgehog pathway proteins.PloS one · 2024Article
- Usability of serum hedgehog signalling proteins as biomarkers in canine mammary carcinomas.BMC veterinary research · 2023Article
- Antitumoral effects of Bortezomib in malignant mesothelioma: evidence of mild endoplasmic reticulum stress in vitro and activation of T cell response in vivo.Biology direct · 2023Article
- The Hedgehog Pathway as a Therapeutic Target in Chronic Myeloid Leukemia.Pharmaceutics · 2023Review
- Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients.Life (Basel, Switzerland) · 2022Article
- Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.Cancers · 2022Review
- Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo.Journal of translational medicine · 2022Article
- Expression of yes-associated protein, β-catenin and smoothened, and their clinical significance in invasive breast cancer.Experimental and therapeutic medicine · 2022Article
- Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy.Investigational new drugs · 2022Review
- Evaluation of Hedgehog Pathway Inhibitors as a Therapeutic Option for Uterine Leiomyosarcoma Using the Xenograft Model.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance.International journal of molecular sciences · 2022Review
- Breast cancer: molecular mechanisms of underlying resistance and therapeutic approaches.American journal of cancer research · 2022Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog (Shh) and NF-κB expression in 51 breast cancer (ductal carcinoma) tissues using immunohistochemistry. We found a positive correlation between nuclear GLI1 expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining significantly correlated with a lower tumor grade. Next, the in vitro effects of two Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT-61. GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21-Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased the nuclear translocation of NF-κB. However, GANT-61 exerted these effects more effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT-61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of TUBO cells in BALB/c mice to different extents. These findings suggest that targeting the Hh pathway using antagonists that act downstream of SMO is a more efficient strategy than using antagonists that act upstream of SMO for interrupting Hh signaling in breast cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.