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Specific protein 1(SP1) regulates the epithelial-mesenchymal transition via lysyl oxidase-like 2(LOXL2) in pancreatic ductal adenocarcinoma

 Im-kyung Kim  ;  Yun Sun Lee  ;  Hyung Sun Kim  ;  Seung Myung Dong  ;  Joon Seong Park  ;  Dong Sup Yoon 
 SCIENTIFIC REPORTS, Vol.9(1) : 5933, 2019 
Journal Title
Issue Date
Specific protein 1 (SP1) is associated with aggressive behavior, invasive clinical phenotype and poor clinical outcomes in various cancers. We studied whether SP1 exerts its effect on invasiveness and promotion of the epithelial-mesenchymal transition (EMT) by regulating lysyl oxidase-like 2 (LOXL2) in pancreatic ductal adenocarcinoma (PDAC) cell lines. We showed that silencing of SP1 in MIA Paca-2 cell significantly decreased cell invasion and migration. In MIA Paca-2 cells, silencing of SP1 induced a reduction of LOXL2 expression, whereas LOXL2 silencing did not lead to a decrease in the expression of SP1. Chromatin immunoprecipitation assay demonstrated the binding of SP1 to LOXL2 promoter. Wound healing and transmigration assays also showed that transfection of both SP1 and LOXL2 siRNA induced most significant decrease of cell invasion and migration compared to either SP1 or LOXL2-only silenced cells. Finally, we investigated the prognostic value of SP1 in patients with PDAC and SP1/LOX2 expression was examined by immunochemistry. Univariate and multivariate analyses showed that tumor differentiation and co-expression of SP1 and LOXL2 were independent factors for disease-free survival. In summary, our study demonstrates that SP1 modulates EMT and is involved in tumor invasion and migration of PDAC cells through the regulation of LOXL2.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Im Kyung(김임경) ORCID logo https://orcid.org/0000-0001-8505-5307
Kim, Hyung Sun(김형선) ORCID logo https://orcid.org/0000-0002-9002-3569
Park, Joon Seong(박준성) ORCID logo https://orcid.org/0000-0001-8048-9990
Yoon, Dong Sup(윤동섭) ORCID logo https://orcid.org/0000-0001-6444-9606
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