title: Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation.
abstract: The overexpression of fascin in human carcinomas is associated with aggressive clinical phenotypes and poor prognosis. However, the molecular mechanism underlying the increased expression of fascin in cancer cells is largely unknown. Here, we identified a Sp1 binding element located at -70 to -60 nts of the FSCN1 promoter and validated that Sp1 specifically bound to this element in esophageal carcinoma cells. Fascin expression was enhanced by Sp1 overexpression and blocked by Sp1 RNAi knockdown. Specific inhibition of ERK1/2 decreased phosphorylation levels of Sp1, and thus suppressed the transcription of the FSCN1, resulting in the down-regulation of fascin. Stimulation with EGF could enhance fascin expression via activating the ERK1/2 pathway and increasing phosphorylation levels of Sp1. These data suggest that FSCN1 transcription may be subjected to the regulation of the EGF/EGFR signaling pathway and can be used as a viable biomarker to predict the efficacy of EGFR inhibitors in cancer therapies.
authors.affiliation: Institute of Oncologic Pathology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, No. 22, Xinling Road, Shantou 515041, People's Republic of China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Lu
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
authors.forename: Ze-Peng
authors.initials: ZP
authors.lastname: Du
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Xie
authors.forename: Zhang-Yan
authors.initials: ZY
authors.lastname: Guo
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Gao
authors.forename: Lian-Di
authors.initials: LD
authors.lastname: Liao
authors.forename: Zhong-Ying
authors.initials: ZY
authors.lastname: Shen
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D011506:Proteins; C020324:fascin; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases