{"doi":"10.1016/j.bbrc.2014.12.108","title":"Hedgehog signaling is synergistically enhanced by nutritional deprivation and ligand stimulation in human fibroblasts of Gorlin syndrome","abstract":null,"journal":"Biochemical and Biophysical Research Communications","year":2015,"id":621390,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473935,"name":"Katsunori Fujii","orcid":"0000-0002-8937-0547","position":1,"is_corresponding":false},{"id":394935,"name":"Tadashi Shiohama","orcid":"0000-0003-0076-5882","position":2,"is_corresponding":false},{"id":1604530,"name":"Hideki Uchikawa","orcid":null,"position":3,"is_corresponding":false},{"id":274969,"name":"Naoki Shimojo","orcid":"0000-0002-8076-0493","position":4,"is_corresponding":false},{"id":1604528,"name":"Hiromi Mizuochi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hedgehog signaling is synergistically enhanced by nutritional deprivation and ligand stimulation in human fibroblasts of Gorlin syndrome","abstract":"Hedgehog signaling is a pivotal developmental pathway that comprises hedgehog, PTCH1, SMO, and GLI proteins. Mutations in PTCH1 are responsible for Gorlin syndrome, which is characterized by developmental defects and tumorigenicity. Although the hedgehog pathway has been investigated extensively in Drosophila and mice, its functional roles have not yet been determined in human cells. In order to elucidate the mechanism by which transduction of the hedgehog signal is regulated in human tissues, we employed human fibroblasts derived from three Gorlin syndrome patients and normal controls. We investigated GLI1 transcription, downstream of hedgehog signaling, to assess native signal transduction, and then treated fibroblasts with a recombinant human hedgehog protein with or without serum deprivation. We also examined the transcriptional levels of hedgehog-related genes under these conditions. The expression of GLI1 mRNA was significantly higher in Gorlin syndrome-derived fibroblasts than in control cells. Hedgehog stimulation and nutritional deprivation synergistically enhanced GLI1 transcription levels, and this was blocked more efficiently by vismodegib, a SMO inhibitor, than by the natural compound, cyclopamine. Messenger RNA profiling revealed the increased expression of Wnt signaling and morphogenetic molecules in these fibroblasts. These results indicated that the hedgehog stimulation and nutritional deprivation synergistically activated the hedgehog signaling pathway in Gorlin syndrome fibroblasts, and this was associated with increments in the transcription levels of hedgehog-related genes such as those involved in Wnt signaling. These fibroblasts may become a significant tool for predicting the efficacies of hedgehog molecular-targeted therapies such as vismodegib.","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25576868","pmcid":null,"openalex_id":"https://openalex.org/W2033277150","authors":[],"funders":[{"funder_name":"Ministry of Health, Labor, and Welfare of Japan","grant_id":"21591313","title":null},{"funder_name":"Ministry of Health, Labor, and Welfare of Japan","grant_id":"25282033","title":null},{"funder_name":"Cancer Research Network","grant_id":"","title":null}],"total_grants":3,"fwci":0.551,"citation_percentile":0.66130066,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":2},{"year":2018,"count":1},{"year":2019,"count":2},{"year":2020,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0006291X14023225?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0006291X14023225?httpAccept=text/xml","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bbrc.2014.12.108","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25576868","host_type":"repository"}],"fields_of_study":["Hedgehog Signaling Pathway Studies","Oral and Maxillofacial Pathology","Tumors and Oncological Cases","Anilides","Animals","Basal Cell Nevus Syndrome","Cells, Cultured","Cilia","Culture Media, Serum-Free","Fibroblasts","Hedgehog Proteins","Humans","Ligands","Mice","Pyridines","RNA, Messenger","Receptors, G-Protein-Coupled","Signal Transduction","Smoothened Receptor","Transcription Factors","Veratrum Alkaloids","Zinc Finger Protein GLI1"],"mesh_terms":["Zinc Finger Protein GLI1","Smoothened Receptor","Anilides","Animals","Basal Cell Nevus Syndrome","Cells, Cultured","Cilia","Fibroblasts","Humans","Ligands","Pyridines","RNA, Messenger","Transcription Factors","Veratrum Alkaloids","Signal Transduction","Culture Media, Serum-Free","Receptors, G-Protein-Coupled","Mice","Hedgehog Proteins"],"keywords":["GLI1","Hedgehog signaling pathway","Hedgehog","Wnt signaling pathway","Smoothened","Indian hedgehog","Cyclopamine","Biology","PTCH1","Sonic hedgehog","Cell biology","Signal transduction","GLI2","Endocrinology","Internal medicine","Cancer research","Medicine","Gorlin Syndrome","Hedgehog Pathway","Nevoid Basal Cell Carcinoma Syndrome","Human Fibroblasts"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T14:22:58.752880Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}