Specific protein 1(SP1) regulates the epithelial-mesenchymal transition via lysyl oxidase-like 2(LOXL2) in pancreatic ductal adenocarcinoma
Specific protein 1(SP1) regulates the epithelial-mesenchymal transition via lysyl oxidase-like 2(LOXL2) in pancreatic ductal adenocarcinoma
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DOI：
10.1038/s41598-019-42501-6
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发表时间：
2019-04-11
影响因子：
4.6
通讯作者：
Yoon, Dong Sup
中科院分区：
文献类型：
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作者：
Kim, Im-Kyung;Lee, Yun Sun;Yoon, Dong Sup
特异性蛋白1 （SP1）与多种癌症的侵袭性行为、侵袭性临床表型和不良临床结果相关。我们研究了SP1是否通过调节赖氨酸氧化酶样2 （LOXL2）在胰腺导管腺癌（PDAC）细胞系中发挥侵袭性和促进上皮-间质转化（EMT）的作用。我们发现，在MIA Paca-2细胞中，SP1的沉默显著降低了细胞的侵袭和迁移。在MIA Paca-2细胞中，SP1沉默诱导LOXL2表达减少，而LOXL2沉默不导致SP1表达减少。染色质免疫沉淀法证实SP1与LOXL2启动子结合。伤口愈合和迁移实验也表明，与SP1或仅LOXL2沉默的细胞相比，转染SP1和LOXL2 siRNA诱导的细胞侵袭和迁移的减少最为显著。最后，我们研究SP1在PDAC患者中的预后价值，并通过免疫化学检测SP1/LOX2的表达。单因素和多因素分析显示，SP1和LOXL2的肿瘤分化和共表达是无病生存的独立因素。综上所述，我们的研究表明SP1通过调控LOXL2调控EMT，参与PDAC细胞的肿瘤侵袭和迁移。
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.