ArticleCancer research2009
Epidermal growth factor receptor signaling synergizes with Hedgehog/GLI in oncogenic transformation via activation of the MEK/ERK/JUN pathway.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 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
124 citing papers in PubMed, 210 citations in OpenAlex.
- The Role of Hedgehog Signaling in Non-small Cell Lung Cancer: Targeting Tumor Invasion, Therapy Resistance and Novel Therapeutic Strategies.International journal of biological sciences · 2026Review
- circ-EGFR is a predictor of response to Cetuximab and a potential target in colorectal cancer.EMBO molecular medicine · 2025Article
- Basaloid Cell Hyperplasia Overlying Dermatofibroma.Dermatopathology (Basel, Switzerland) · 2025Article
- An Analysis Regarding the Association Between DAZ Interacting Zinc Finger Protein 1 (DZIP1) and Colorectal Cancer (CRC).Molecular biotechnology · 2025Article
- Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Dietary Polyphenols Effects on Focal Adhesion Plaques and Metalloproteinases in Cancer Invasiveness.Biomedicines · 2024Review
- Positive correlation between the nuclear expression of GPER and pGLI3 in prostate cancer tissues from patients with different Gleason scores.Frontiers in endocrinology · 2024Article
- Novel Approaches in Non-Melanoma Skin Cancers-A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC).Cells · 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
- ALCAM-EGFR interaction regulates myelomagenesis.Blood advances · 2021Article
- Article
- Article
- Targeting K-Ras and apoptosis-driven cellular transformation in cancer.Cell death discovery · 2021Review
- GLI1: A Therapeutic Target for Cancer.Frontiers in oncology · 2021Review
- Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma.Journal of clinical medicine · 2020Review
- Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer.Journal of clinical medicine · 2020Review
- Basal Cell Carcinoma: A Comprehensive Review.International journal of molecular sciences · 2020Review
- Phosphoproteomics of short-term hedgehog signaling in human medulloblastoma cells.Cell communication and signaling : CCS · 2020Article
- Small Molecule Intervention in a Protein Kinase C-Gli Transcription Factor Axis.ACS chemical biology · 2020Article
- Article
64 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
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Persistent activation of the Hedgehog (HH)/GLI signaling pathway has been implicated in the development of a number of human cancers. The GLI zinc finger transcription factors act at the end of the HH signaling cascade to control gene expression, and recent studies have shown that the activity of GLI proteins can be additionally modified by integration of distinct signals, such as the MEK/extracellular signal-regulated kinase (ERK) and phosphinositide-3 kinase (PI3K)/AKT pathway. However, little is known about the identity of the upstream activators of these HH/GLI interacting signaling pathways in cancer. Here, we provide evidence that integration of the HH/GLI and epidermal growth factor receptor (EGFR) pathway synergistically induces oncogenic transformation, which depends on EGFR-mediated activation of the RAS/RAF/MEK/ERK but not of the PI3K/AKT pathway. EGFR/MEK/ERK signaling induces JUN/activator protein 1 activation, which is essential for oncogenic transformation, in combination with the GLI activator forms GLI1 and GLI2. Furthermore, pharmacologic inhibition of EGFR and HH/GLI efficiently reduces growth of basal cell carcinoma (BCC) cell lines derived from mice with activated HH/GLI signaling. The results identify the synergistic integration of GLI activator function and EGFR signaling as a critical step in oncogenic transformation and provide a molecular basis for therapeutic opportunities relying on combined inhibition of the HH/GLI and EGFR/MEK/ERK/JUN pathway in BCC.
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.