scholarly journals Role of FGFR2c and Its PKCε Downstream Signaling in the Control of EMT and Autophagy in Pancreatic Ductal Adenocarcinoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4993
Author(s):  
Danilo Ranieri ◽  
Luisa Guttieri ◽  
Salvatore Raffa ◽  
Maria Rosaria Torrisi ◽  
Francesca Belleudi
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Intracellular Signaling ◽  
Specific Protein ◽  
Ductal Adenocarcinoma ◽  
Aberrant Expression ◽  
Downstream Signaling ◽  
Adenocarcinoma Cells ◽  
Autophagic Process ◽  
Signaling Activation

Pancreatic ductal adenocarcinoma (PDAC) is a treatment-resistant malignancy characterized by a high malignant phenotype including acquired EMT signature and deregulated autophagy. Since we have previously described that the aberrant expression of the mesenchymal FGFR2c and the triggering of the downstream PKCε signaling are involved in epidermal carcinogenesis, the aim of this work has been to assess the contribution of these oncogenic events also in the pancreatic context. Biochemical, molecular and immunofluorescence approaches showed that FGFR2c expression impacts on PDAC cell responsiveness to FGF2 in terms of intracellular signaling activation, upregulation of EMT-related transcription factors and modulation of epithelial and mesenchymal markers compatible with the pathological EMT. Moreover, shut-off via specific protein depletion of PKCε signaling, activated by high expression of FGFR2c resulted in a reversion of EMT profile, as well as in a recovery of the autophagic process. The detailed biochemical analysis of the intracellular signaling indicated that PKCε, bypassing AKT and directly converging on ERK1/2, could be a signaling molecule downstream FGFR2c whose inhibition could be considered as possible effective therapeutic approach in counteracting aggressive phenotype in cancer.

Abstract 271: The role of ATM and DNA-PK in responding to AZD6738-induced damage in pancreatic ductal adenocarcinoma cells

2019 ◽  
Author(s):  
Charles R. Dunlop ◽  
Yann Wallez ◽  
Sandra Bernaldo de Quirós Fernández ◽  
Saadia A. Karim ◽  
Alan Lau ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells

Abstract 271: The role of ATM and DNA-PK in responding to AZD6738-induced damage in pancreatic ductal adenocarcinoma cells

2019 ◽  
Author(s):  
Charles R. Dunlop ◽  
Yann Wallez ◽  
Sandra Bernaldo de Quirós Fernández ◽  
Saadia A. Karim ◽  
Alan Lau ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells

scholarly journals CCAAT/Enhancer-Binding Protein Delta (C/EBPδ): A Previously Unrecognized Tumor Suppressor that Limits the Oncogenic Potential of Pancreatic Ductal Adenocarcinoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2546
Author(s):  
Leonie Hartl ◽  
JanWillem Duitman ◽  
Hella L. Aberson ◽  
Kan Chen ◽  
Frederike Dijk ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Suppressor ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Binding Protein ◽  
Ductal Adenocarcinoma ◽  
Ductal Cells ◽  
Enhancer Binding Protein ◽  
Adenocarcinoma Cells ◽  
Ccaat Enhancer Binding Protein

CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. We determined C/EBPδ expression in biopsies from pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft agar assays. We thus report a previously unrecognized but important tumor suppressor role of C/EBPδ in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal adenocarcinoma, although the latter claim needs to be substantiated in future studies.

scholarly journals Role of H + /K + ‐ATPase and Na + /Ca 2+ exchangers in pancreatic ductal adenocarcinoma cells

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Andrea Giannuzzo ◽  
Jing Wang ◽  
Else Kay Hoffman ◽  
Stine Helene Pedersen ◽  
Ivana Novak
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells

The role of exosomes in promoting acquired resistance to gemcitabine and nanoparticle albumin-bound (NAB) paclitaxel in pancreatic ductal adenocarcinoma cells.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23253-e23253
Author(s):  
Moh'd M. Khushman ◽  
Girijesh K. Patel ◽  
Arun Bhardwaj ◽  
Sanjeev K. Srivastava ◽  
Mohammad Aslam Khan ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Acquired Resistance ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells

scholarly journals Histone demethylase JMJD3 disrupts spectrin-dependent cytoskeleton in Pancreatic Ductal Adenocarcinoma cells by regulating H exokinase domain containing 1 expression

2020 ◽  
Author(s):  
Zhangang Xiao ◽  
Jing Shen ◽  
Qijie Zhao ◽  
Shixin Xiang ◽  
Yinxin Zhu ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ectopic Expression ◽  
Histone Demethylase ◽  
Ductal Adenocarcinoma ◽  
Histone 3 ◽  
Adenocarcinoma Cells ◽  
Cytoskeleton Disruption ◽  
Demethylation Activity

Abstract Background: JMJD3 is a jmjd domain containing histone demethylase which can remove methyl groups from lysine 27 of histone 3 (H3K27) to active histone methylated genes. Previous studies have demonstrated that JMJD3 played a crucial role in inflammation. Methods: Our study showed that JMJD3 was significantly down-regulated in pancreatic ductal adenocarcinoma (PDAC) cell lines and tissues. Restored expression of JMJD3 inhibited oncogenic phenotypes of PDAC cells, including cell proliferation, cell migration, and in vivo tumorigenicity, indicating a tumor suppressive role. Gene-expression microarray revealed that Hexokinase domain containing 1 (HKDC1) was one of the JMJD3 downstream targets. Results: The expression of JMJD3 and HKDC1 in PDAC tissues was positively correlated. High H3K27 tri-methylation (H3K27me3) status in HKDC1 gene was attenuated by ectopic expression of JMJD3 in PDAC cells, suggested that JMJD3 regulated HKDC1 expression by histone demethylation activity. The tumor suppressive role of HKDC1 in PDAC was also proved. Moreover, HKDC1 was demonstrated to competitively bind to spectrin beta Ⅱ to induce cytoskeleton disruption, which may contribute to tumor suppression. Conclusion: Taken together, our study indicates that JMJD3 may disrupt spectrin-dependent cytoskeleton via activation of HKDC1 to suppress PDAC.

scholarly journals Effect of miR-184 on Proliferation and Apoptosis of Pancreatic Ductal Adenocarcinoma and Its Mechanism

2020 ◽  
Vol 19 ◽  
pp. 153303382094323
Author(s):  
Shentao Li ◽  
He Li ◽  
Weiwei Ge ◽  
Kai Song ◽  
Chunyu Yuan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Caspase 3 ◽  
Survival Curve ◽  
Ductal Adenocarcinoma ◽  
Control Group ◽  
Caspase 9 ◽  
Tumor Tissues ◽  
Adenocarcinoma Cells

Objective: Previous studies have shown that abnormal expression of microRNA-184 leads to a variety of cancers, including pancreatic ductal adenocarcinoma, suggesting microRNA-184 as a new treatment target for pancreatic ductal adenocarcinoma. However, the molecular mechanism of microRNA-184 in pancreatic ductal adenocarcinoma remains unclear. It is important to investigate the effect and role of microRNA-184 in pancreatic ductal adenocarcinoma. Methods: The clinical and laboratory inspection data of 120 patients with pancreatic cancer admitted to the First Affiliated Hospital of Anhui Medical University were compared. MicroRNA-184 expression in tumor tissues and cells was evaluated using reverse transcription polymerase chain reaction. Flow cytometry and Annexin V/propidium iodide staining were performed to examine cell cycle and apoptosis. Western blotting analysis was conducted to measure the protein expression of p-PI3K, p-AKT, JNK1, C-Myc, C-Jun, caspase-9, and caspase-3. Results: MicroRNA-184 expression was low in patients with pancreatic ductal adenocarcinoma. Survival curve showed that patients with lower expression of microRNA-184 in tumor tissues had a worse prognosis and shorter survival time ( P < .05), and the multivariate analysis identified that microRNA-184 was an independent prognostic indicator ( P < .05). In vitro studies showed that microRNA-184 overexpression induced apoptosis and suppressed cell cycle transition from G1 to S and G2 phases in pancreatic ductal adenocarcinoma cells. Furthermore, molecular studies revealed that inhibition of microRNA-184 promoted the gene expression of p-PI3K, p-AKT, JNK1, C-Myc, and C-Jun compared with the control group. Overexpression of microRNA-184 led to significantly increased expression of caspase-9 and caspase-3 and significantly decreased expression of Bcl-2. Conclusion: This study suggests that microRNA-184 inhibits the proliferation and promotes the apoptosis of pancreatic ductal adenocarcinoma cells by downregulating the expression of C-Myc, C-Jun, and Bcl-2. Our verification of the role of microRNA-184 may provide a novel biomarker for the diagnosis, therapy, and prognosis of pancreatic ductal adenocarcinoma.

The Anti-Tumor Activity of Afatinib in Pancreatic Ductal Adenocarcinoma Cells

2020 ◽  
Vol 20 (12) ◽  
pp. 1447-1458
Author(s):  
Zhenyu Ye ◽  
Yecheng Li ◽  
Jiaming Xie ◽  
Zhenyu Feng ◽  
Xiaodong Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Underlying Mechanism ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
The Social ◽  
New Perspective

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is the most common form of pancreatic cancer and leading causes of pancreatic cancer death because of most PDAC patients with advanced unresectable disease at that time, which is remarkably resistant to all forms of chemotherapy and radiotherapy. Objective: PDAC increases the social and patient's family burden. However, the PDAC pathogenesis is not identified. We are trying to uncover the underlying mechanism in the future. Methods: In our research, the drug-resistant cell line was successfully induced in the vitro by progressive concentrations of Afatinib, which we named it as BxPC3-AR. Results: It has been observed that the effect of autophagy was on the resistance of BxPC3-AR to Afatinib. Conclusion: It has been confirmed that autophagy plays a certain role in BxPC3-AR resistance to Afatinib. Our findings provide a new perspective on the role of autophagy in pancreatic ductal adenocarcinoma.

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