title: Association between high levels of Notch3 expression and high invasion and poor overall survival rates in pancreatic ductal adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is a commonly fatal tumour. It is characterized by early metastasis and high mortality. Many patients die as a result of PDAC tumour progression. However, the underlying mechanism of invasion and metastasis in PDAC is still not fully understood. Previous studies showed that the Notch signalling pathway may play an important role in the progression of tumour invasion and metastasis. However, it is not yet known whether the Notch signalling pathway participates in the progression of invasion in PDAC. In the present study, immunohistochemistry showed that a high expression of Notch3 was correlated with tumour grade, metastasis, venous invasion and American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage. Kaplan-Meier curves suggested that a high expression of Notch3 was a significant risk factor for shortened survival time. We also showed that inhibition of Notch3 had an anti‑invasion role in PDAC cells. In vitro, the inhibition of Notch3 reduced the migration and invasion capabilities of PDAC cells by regulating the expressions of E-cadherin, CD44v6, MMP-2, MMP-9, VEGF and uPA via regulating the COX-2 and ERK1/2 pathways. These results indicated that downregulation of the Notch signalling pathway may be a novel and useful approach for preventing and treating PDAC invasion.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Tumor Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Jin-Xue
authors.initials: JX
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The 155 Central Hospital of PLA, Kaifeng, Henan 471000, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Tumor Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Tumor Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of General Surgery, First People's Hospital, Xiang Xin, Henan 453000, P.R. China.
authors.forename: Pei-Min
authors.initials: PM
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The 155 Central Hospital of PLA, Kaifeng, Henan 471000, P.R. China.
authors.forename: Er-Feng
authors.initials: EF
authors.lastname: Li
authors.affiliation: Department of General Surgery, The 155 Central Hospital of PLA, Kaifeng, Henan 471000, P.R. China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Gong
authors.affiliation: Department of General Surgery, The 155 Central Hospital of PLA, Kaifeng, Henan 471000, P.R. China.
authors.forename: Ming-Wen
authors.initials: MW
authors.lastname: Kou
authors.affiliation: Department of General Surgery, The 155 Central Hospital of PLA, Kaifeng, Henan 471000, P.R. China.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Gou
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shannxi 710032, P.R. China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D000071656:Receptor, Notch3 / Q000096:biosynthesis* / Q000235:genetics; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C499374:NOTCH3 protein, human; D009363:Neoplasm Proteins; D000071656:Receptor, Notch3