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.
CCR7 Twist EMT PDAC
This is a preview of subscription content, log in to check access
This study was supported by grants to BFX from Foundation of Jilin Provincial Science & Technology Department [No. 201201044].
Helm O, Mennrich R, Petrick D, et al. Comparative characterization of stroma cells and ductal epithelium in chronic pancreatitis and pancreatic ductal adenocarcinoma. PLoS One. 2014;9(5):e94357.CrossRefPubMedPubMedCentralGoogle Scholar
Chee CE, Krishnamurthi S, Nock CJ, et al. Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas. Oncologist. 2013;18(10):1091–2.CrossRefPubMedPubMedCentralGoogle Scholar
Distler M, Kersting S, Niedergethmann M, et al. Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg. 2013;258(2):324–30.CrossRefPubMedGoogle Scholar
Laghi L, Beghelli S, Spinelli A, et al. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma. PLoS One. 2012;7(9):e46002.CrossRefPubMedPubMedCentralGoogle Scholar
Comerford I, Harata-Lee Y, Bunting MD, et al. A myriad of functions and complex regulation of the CCR7/CCL19/CCL21 chemokine axis in the adaptive immune system. Cytokine Growth Factor Rev. 2013;24(3):269–83.CrossRefPubMedGoogle Scholar
Hausmann S, Kong B, Michalski C, et al. The role of inflammation in pancreatic cancer. Adv Exp Med Biol. 2014;816:129–51.CrossRefPubMedGoogle Scholar
Lee WT, Lee TH, Cheng CH, et al. Antroquinonol from antrodia camphorata suppresses breast tumor migration/invasion through inhibiting ERK-AP-1- and AKT-NF-κB-dependent MMP-9 and epithelial-mesenchymal transition expressions. Food Chem Toxicol. 2015.Google Scholar
Qu BL, Yu W, Huang YR, et al. 6-OH-BDE-47 promotes human lung cancer cells epithelial mesenchymal transition via the AKT/Snail signal pathway. Environ Toxicol Pharmacol. 2014;39:271–9.CrossRefPubMedGoogle Scholar