ArticleOncogene2004
IFNalpha induces Fas expression and apoptosis in hedgehog pathway activated BCC cells through inhibiting Ras-Erk signaling.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 60 citations in OpenAlex.
- STING Signaling and Skin Cancers.Cancers · 2021Review
- Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.Molecular carcinogenesis · 2017Review
- Chelerythrine chloride induces apoptosis in renal cancer HEK-293 and SW-839 cell lines.Oncology letters · 2016Article
- FoxO3a nuclear localization and its association with β-catenin and Smads in IFN-α-treated hepatocellular carcinoma cell lines.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Article
- Cutaneous carcinosarcoma: further insights into its mutational landscape through massive parallel genome sequencing.Virchows Archiv : an international journal of pathology · 2014Article
- Hedgehog signalling pathway: carcinogenesis and targeted therapy.Iranian journal of cancer prevention · 2013Review
- A role for transcription factor STAT3 signaling in oncogene smoothened-driven carcinogenesis.The Journal of biological chemistry · 2012Article
- A population-based study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another cancer.Cancer epidemiology · 2012Article
- Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner.Cellular signalling · 2012Article
- Hedgehog signaling drives cellular survival in human colon carcinoma cells.Cancer research · 2011Article
- Activation of the Hedgehog pathway in chronic myelogeneous leukemia patients.Journal of experimental & clinical cancer research : CR · 2011Article
- Toll-like receptor 3 regulates neural stem cell proliferation by modulating the Sonic Hedgehog pathway.PloS one · 2011Article
- Basal cell carcinomas: attack of the hedgehog.Nature reviews. Cancer · 2008Review
- Review
- Smoothened signal transduction is promoted by G protein-coupled receptor kinase 2.Molecular and cellular biology · 2006Article
- Adenovirus delivery provides extended interferon-alpha exposure and augments treatment of metastatic carcinoma.Cancer gene therapy · 2006Article
- Mechanisms of type-I- and type-II-interferon-mediated signalling.Nature reviews. Immunology · 2005Review
- Antiviral treatment with alpha interferon up-regulates CD14 on liver macrophages and its soluble form in patients with chronic hepatitis B.Antimicrobial agents and chemotherapy · 2005Article
- Interferons alpha and gamma induce p53-dependent and p53-independent apoptosis, respectively.Oncogene · 2005Article
- Activation of the hedgehog pathway in advanced prostate cancer.Molecular cancer · 2004Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Basal cell carcinoma (BCC), the most common form of human cancer, is understood to be associated with activation of the sonic hedgehog pathway, through loss-of-function mutations of tumor suppressor PTCH1 or gain-of-function mutations of smoothened. Interferon (IFN)-based therapy is quite effective in BCC treatment, but the molecular basis is not well understood. Here we report a novel mechanism by which IFNalpha mediates apoptosis in BCCs. In the presence of IFNalpha, we observed increased apoptosis in a BCC cell line ASZ001, in which PTC is null, and therefore with constitutive activation of the sonic hedgehog pathway. We demonstrate that SMO agonist Ag-1.4 mediates activation of extracellular signal-regulated kinase (Erk) phosphorylation, which is abrogated by IFNalpha in sonic hedgehog responsive C3H10T1/2 cells. In transient transfection experiments, we demonstrate that IFNalpha inhibits Erk phosphorylation and serum response element activation induced by expression of SMO, Gli1, PDGFRalpha and activated Raf, but not activated mitogen-activated Erk-regulating kinase (Mek), suggesting that IFNalpha targets mainly on Mek function. We further show that IFNalpha induces expression of Fas in BCC cells through interfering with Mek function. The role of the Fas-L/Fas signaling axis in IFNalpha-mediated apoptosis is demonstrated by the fact that addition of Fas-L neutralizing antibodies, just as caspase-8 inhibitor Z-IETD-FMK, effectively prevents IFNalpha-mediated apoptosis. Thus, our data indicate that IFNalpha-based BCC therapy induces Fas expression and apoptosis through interfering with Mek function.
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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.