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.
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.
Lu
Xiao-Feng
XF
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.
Li
En-Min
EM
Du
Ze-Peng
ZP
Xie
Jian-Jun
JJ
Guo
Zhang-Yan
ZY
Gao
Shu-Ying
SY
Liao
Lian-Di
LD
Shen
Zhong-Ying
ZY
Xie
Dong
D
Xu
Li-Yan
LY
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
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