ArticleInternational journal of cancer2018
Synergistic cross-talk of hedgehog and interleukin-6 signaling drives growth of basal cell carcinoma.
Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Cooperative Hedgehog/GLI and JAK/STAT signaling drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer.Cell communication and signaling : CCS · 2025Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Sonic hedgehog pathway for the treatment of inflammatory diseases: implications and opportunities for future research.Journal for immunotherapy of cancer · 2022Article
- The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis.Biomedicines · 2021Review
- Article
- Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage.Cell communication and signaling : CCS · 2021Review
- Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment.Acta pharmaceutica Sinica. B · 2021Review
- Cancer stem cells and macrophages: molecular connections and future perspectives against cancer.Oncotarget · 2021Review
- Hedgehog Signaling: Implications in Cancers and Viral Infections.International journal of molecular sciences · 2021Review
- Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma.Journal of clinical medicine · 2020Review
- Epidermal activation of Hedgehog signaling establishes an immunosuppressive microenvironment in basal cell carcinoma by modulating skin immunity.Molecular oncology · 2020Article
- Article
- Phosphoproteomics of short-term hedgehog signaling in human medulloblastoma cells.Cell communication and signaling : CCS · 2020Article
- Hedgehog/GLI signaling in tumor immunity - new therapeutic opportunities and clinical implications.Cell communication and signaling : CCS · 2019Review
- Review
- Overexpression of Desmoglein 2 in a Mouse Model of Gorlin Syndrome Enhances Spontaneous Basal Cell Carcinoma Formation through STAT3-Mediated Gli1 Expression.The Journal of investigative dermatology · 2019Article
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistent activation of hedgehog (HH)/GLI signaling accounts for the development of basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer with rising incidence. Targeting HH/GLI signaling by approved pathway inhibitors can provide significant therapeutic benefit to BCC patients. However, limited response rates, development of drug resistance, and severe side effects of HH pathway inhibitors call for improved treatment strategies such as rational combination therapies simultaneously inhibiting HH/GLI and cooperative signals promoting the oncogenic activity of HH/GLI. In this study, we identified the interleukin-6 (IL6) pathway as a novel synergistic signal promoting oncogenic HH/GLI via STAT3 activation. Mechanistically, we provide evidence that signal integration of IL6 and HH/GLI occurs at the level of cis-regulatory sequences by co-binding of GLI and STAT3 to common HH-IL6 target gene promoters. Genetic inactivation of Il6 signaling in a mouse model of BCC significantly reduced in vivo tumor growth by interfering with HH/GLI-driven BCC proliferation. Our genetic and pharmacologic data suggest that combinatorial HH-IL6 pathway blockade is a promising approach to efficiently arrest cancer growth in BCC patients.
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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.