scholarly journals Deubiquitinase inhibitor degrasyn suppresses metastasis by targeting USP5‐WT1‐E‐cadherin signalling pathway in pancreatic ductal adenocarcinoma

2019 ◽  
Vol 24 (2) ◽  
pp. 1370-1382 ◽  
Author(s):  
Jiajia Li ◽  
Haiying Li ◽  
Weijian Zhu ◽  
Bin Zhou ◽  
Jianchao Ying ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Signalling Pathway ◽  
Ductal Adenocarcinoma ◽  
E Cadherin

Loss of e-cadherin and β-catenin expression correlate with poor prognosis in patients with resectable pancreatic ductal adenocarcinoma

Pancreatology ◽  
2012 ◽  
Vol 12 (3) ◽  
pp. e5
Author(s):  
Nigel B. Jamieson ◽  
Karin A. Oien ◽  
Euan J. Dickson ◽  
Colin J. McKay ◽  
C. Ross Carter
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Ductal Adenocarcinoma ◽  
E Cadherin

scholarly journals Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines: The Role of Neutrophils and Neutrophil-Derived Elastase

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Thomas Große-Steffen ◽  
Thomas Giese ◽  
Nathalia Giese ◽  
Thomas Longerich ◽  
Peter Schirmacher ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Pancreatic Tumor ◽  
Polymorphonuclear Neutrophils ◽  
Nuclear Accumulation ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition ◽  
E Cadherin

Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT) is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN) and the tumor cell transition, biopsies of patients with PDAC (n=115) were analysed with regard to PMN infiltration and nuclear expression ofβ-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation ofβ-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated,β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMTin vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and—by implication—to tumor progression is possible.

scholarly journals E-cadherin expression in obesity-associated, Kras-initiated pancreatic ductal adenocarcinoma in mice

Surgery ◽  
2015 ◽  
Vol 158 (6) ◽  
pp. 1564-1572 ◽  
Author(s):  
Alexander P. Stark ◽  
Hui-Hua Chang ◽  
Xiaoman Jung ◽  
Aune Moro ◽  
Kathleen Hertzer ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
E Cadherin

scholarly journals Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

2018 ◽  
Vol 18 (3) ◽  
pp. 246-251 ◽  
Author(s):  
Petra Radulović ◽  
Božo Krušlin
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Patient Survival ◽  
Negative Impact ◽  
Prognostic Significance ◽  
Pancreatic Tissue ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Rank Test ◽  
Normal Pancreatic Tissue ◽  
E Cadherin

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.

Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma

2016 ◽  
Vol 70 (7) ◽  
pp. 619-624 ◽  
Author(s):  
Aya Kawanishi ◽  
Kenichi Hirabayashi ◽  
Misuzu Yamada ◽  
Yumi Takanashi ◽  
Atsuko Hadano ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tissue Microarray ◽  
Histological Grade ◽  
Tumour Size ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Clinicopathological Significance ◽  
E Cadherin

AimsThe loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsImmunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained.ResultsNecl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p<0.001). Negative Necl-4 expression was significantly associated with a larger tumour size of >30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB–IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, p<0.001).ConclusionsThe results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.

Restoration of E-cadherin expression in pancreatic ductal adenocarcinoma treated with microRNA-101

Surgery ◽  
2012 ◽  
Vol 152 (4) ◽  
pp. 704-713 ◽  
Author(s):  
Aamer M. Qazi ◽  
Oksana Gruzdyn ◽  
Assaad Semaan ◽  
Shelly Seward ◽  
Sreedhar Chamala ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
E Cadherin

scholarly journals Understanding the Mechanism of Cell Death in Gemcitabine Resistant Pancreatic Ductal Adenocarcinoma: A Systems Biology Approach

2020 ◽  
Vol 20 (7) ◽  
pp. 483-490 ◽  
Author(s):  
Imlimaong Aier ◽  
Pritish K. Varadwaj
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Systems Biology ◽  
Cell Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signalling Pathway ◽  
Ductal Adenocarcinoma ◽  
Apoptosis Pathway ◽  
Pathway Models ◽  
Cell Growth And Proliferation

Background: Gemcitabine is the standard chemotherapeutic drug administered in advanced Pancreatic Ductal Adenocarcinoma (PDAC). However, due to drug resistance in PDAC patients, this treatment has become less effective. Over the years, clinical trials for the quest of finding novel compounds that can be used in combination with gemcitabine have met very little success. Objective: To predict the driving factors behind pancreatic ductal adenocarcinoma, and to understand the effect of these components in the progression of the disease and their contribution to cell growth and proliferation. Methods: With the help of systems biology approaches and using gene expression data, which is generally found in abundance, dysregulated elements in key signalling pathways were predicted. Prominent dysregulated elements were integrated into a model to simulate and study the effect of gemcitabine- induced hypoxia. Results: In this study, several transcription factors in the form of key drivers of cancer-related genes were predicted with the help of CARNIVAL, and the effect of gemcitabine-induced hypoxia on the apoptosis pathway was shown to have an effect on the downstream elements of two primary pathway models; EGF/VEGF and TNF signalling pathway. Conclusion: It was observed that EGF/VEGF signalling pathway played a major role in inducing drug resistance through cell growth, proliferation, and avoiding cell death. Targeting the major upstream components of this pathway could potentially lead to successful treatment.

scholarly journals Expression of the E-cadherin-catenin complex in patients with pancreatic ductal adenocarcinoma.

2010 ◽  
Vol 48 (1) ◽  
Author(s):  
Anna Pryczynicz ◽  
Katarzyna Guzińska-Ustymowicz ◽  
Andrzej Kemona ◽  
Jolanta Czyzewska
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
E Cadherin
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