title: CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma.
abstract: As reported, the CC chemokine receptor 7 (CCR7) trigger a series of signaling cascades in the epithelial-mesenchymal transition (EMT) of some malignancies. Meanwhile, Twist promotes EMT in pancreatic ductal adenocarcinoma (PDAC) progression. Here, effects of Twist on CCR7-induced EMT in the PDAC were investigated in detail. The immunohistochemistry was used to detect the expression of Twist, and then, in vitro assays were applied. The expression rate of Twist was 72.0 % in PDAC samples and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When PDAC cell line PANC1 was subjected to CCL19 stimulation, the expression of p-ERK, p-AKT, Twist, N-cadherin, MMP9, and α-smooth muscle actin (α-SMA) was induced, while the GSK1120212, BEZ235, and MK2206 prohibited the increase of Twist and EMT biomarkers. For another thing, the si-Twist treatment attenuated CCL19-stimulated EMT occurrence, migration, and invasion phenotypes of PANC1 cells. In conclusion, CCR7 pathway up-regulates Twist expression via ERK and PI3K/AKT signaling to manage the EMT of PDAC. Our work allows for clinical gene or protein-targeted regimen of PDAC patients in the near future.
authors.affiliation: Department of Endocrinology, People's Hospital of Jilin Province, Changchun, 130021, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Xu
authors.affiliation: Changchun Emergency Center, Changchun, 130021, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China. liur@jlu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D054415:Chemokine CCL19 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*
chemical_list: C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CCR7; EMT; PDAC; Twist