scholarly journals TRIM29 as a Novel Biomarker in Pancreatic Adenocarcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hongli Sun ◽  
Xianwei Dai ◽  
Bing Han
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Multivariate Logistic Regression Analysis ◽  
Immunohistochemical Analysis ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion ◽  
Tripartite Motif

Background and Aim. Tripartite motif-containing 29 (TRIM29) is structurally a member of the tripartite motif family of proteins and is involved in diverse human cancers. However, its role in pancreatic cancer remains unclear.Methods. The expression pattern of TRIM29 in pancreatic ductal adenocarcinoma was assessed by immunocytochemistry. Multivariate logistic regression analysis was used to investigate the association between TRIM29 and clinical characteristics.In vitroanalyses by scratch wound healing assay and invasion assays were performed using the pancreatic cancer cell lines.Results. Immunohistochemical analysis showed TRIM29 expression in pancreatic cancer tissues was significantly higher  (n=186)than that in matched adjacent nontumor tissues. TRIM29 protein expression was significantly correlated with lymph node metastasis(P=0.019). Patients with positive TRIM29 expression showed both shorter overall survival and shorter recurrence-free survival than those with negative TRIM29 expression. Multivariate analysis revealed that TRIM29 was an independent factor for pancreatic cancer over survival (HR=2.180, 95% CI: 1.324–4.198,P=0.011).In vitro,TRIM29 knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration, and invasion.Conclusions. Our results indicate that TRIM29 promotes tumor progression and may be a novel prognostic marker for pancreatic ductal adenocarcinoma.

scholarly journals KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jing Chen ◽  
Cui-Cui Zhao ◽  
Fei-Ran Chen ◽  
Guo-Wei Feng ◽  
Fei Luo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
High Expression ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

scholarly journals Transcriptional regulation of SLIT2 expression in pancreatic cancer cell lines

2020 ◽  
Author(s):  
Brenna A. Rheinheimer ◽  
Lukas Vrba ◽  
Bernard W Futscher ◽  
Ronald L Heimark
Keyword(s):  
Pancreatic Cancer ◽  
Transcriptional Regulation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Trichostatin A ◽  
Cancer Cell Lines ◽  
Ductal Adenocarcinoma ◽  
Liver Cancers

AbstractBackgroundSLIT2 has been shown to serve as a tumor suppressor in breast, lung, colon, and liver cancers. Additionally, expression of SLIT2 has been shown to be epigenetically regulated in prostate cancer. Therefore, we sought to determine transcriptional regulation of SLIT2 in pancreatic ductal adenocarcinoma.MethodsRNA expression of SLIT2, SLIT3, and ROBO1 was examined in a panel of pancreatic ductal adenocarcinoma cell lines while protein expression of ROBO1 and SLIT2 was examined in tumor tissue. Methylation of the SLIT2 promoter was determined using Sequenom while histone modifications were queried by chromatin immunoprecipitation. Reexpression of SLIT2 was tested by treatment with 5-aza-2’deoxycytidine and Trichostatin A.ResultsPancreatic cancer cell lines fall into three distinct groups based on SLIT2 and ROBO1 expression. The SLIT2 promoter is methylated in pancreatic ductal adenocarcinoma and SLIT2 expression is dependent on the level of methylation at specific CpG sites. Treatment with 5-aza-2’deoxycytidine (but not Trichostatin A) led to SLIT2 reexpression. The SLIT2 promoter is bivalent in pancreatic ductal adenocarcinoma and histone marks around the transcriptional start site are responsible for transcription.ConclusionsLoss of SLIT2 expression modulated by epigenetic silencing may play a role in pancreatic ductal adenocarcinoma progression.

scholarly journals Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer

2016 ◽  
Vol 310 (11) ◽  
pp. G1124-G1137 ◽  
Author(s):  
Christina Vorvis ◽  
Maria Hatziapostolou ◽  
Swapna Mahurkar-Joshi ◽  
Marina Koutsioumpa ◽  
Jennifer Williams ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Transcription Factors ◽  
Tumor Suppressor ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion ◽  
Network Analyses ◽  
Invasion Mechanisms

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with low survival rates and limited therapeutic options. Thus elucidation of signaling pathways involved in PDAC pathogenesis is essential for identifying novel potential therapeutic gene targets. Here, we used a systems approach to elucidate those pathways by integrating gene and microRNA profiling analyses together with CRISPR/Cas9 technology to identify novel transcription factors involved in PDAC pathogenesis. FOXA2 transcription factor was found to be significantly downregulated in PDAC relative to control pancreatic tissues. Functional experiments revealed that FOXA2 has a tumor suppressor function through inhibition of pancreatic cancer cell growth, migration, invasion, and colony formation. In situ hybridization analysis revealed miR-199a to be significantly upregulated in pancreatic cancer. Bioinformatics and luciferase analyses showed that miR-199a negatively but directly regulates FOXA2 expression through binding in its 3′-untranslated region (UTR). Evaluation of the functional importance of miR-199a on pancreatic cancer revealed that miR-199a acts as an inhibitor of FOXA2 expression, inducing an increase in pancreatic cancer cell proliferation, migration, and invasion. Additionally, gene ontology and network analyses in PANC-1 cells treated with a small interfering RNA (siRNA) against FOXA2 revealed an enrichment for cell invasion mechanisms through PLAUR and ERK activation. FOXA2 deletion (FOXA2Δ) by using two CRISPR/Cas9 vectors in PANC-1 cells induced tumor growth in vivo resulting in upregulation of PLAUR and ERK pathways in FOXA2Δ xenograft tumors. We have identified FOXA2 as a novel tumor suppressor in pancreatic cancer and it is regulated directly by miR-199a, thereby enhancing our understanding of how microRNAs interplay with the transcription factors to affect pancreatic oncogenesis.

Corn silk crude polysaccharide exerts anti-pancreatic cancer activity by blocking the EGFR/PI3K/AKT/CREB signaling pathway

2020 ◽  
Vol 11 (8) ◽  
pp. 6961-6970
Author(s):  
Hong Tao ◽  
Xia Chen ◽  
Zhenyun Du ◽  
Kan Ding
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Cancer Cell Migration ◽  
Corn Silk ◽  
Crude Polysaccharide

S1, a crude polysaccharide from corn silk, may significantly inhibit pancreatic cancer cell proliferation in vitro and in vivo. It can induce apoptosis, arrest the cell cycle in S phase and impede pancreatic cancer cell migration and invasion.

scholarly journals GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Weiliang Jiang ◽  
Congying Chen ◽  
Li Huang ◽  
Jie Shen ◽  
Lijuan Yang
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Pancreatic Cancer Cell ◽  
Differential Expression Analysis ◽  
Ductal Adenocarcinoma ◽  
Cancer Cell Invasion ◽  
Dibutyltin Dichloride ◽  
Inflammatory Stimuli

Cancer-associated inflammation is a key molecular feature in the progression of pancreatic ductal adenocarcinoma (PDAC). GATA4 is a transcription factor that participates in the regulation and normal development of several endoderm- and mesoderm-derived tissues such as the pancreas. However, it remains unclear whether GATA4 is involved in the inflammation-driven development of pancreatic cancer. Here, we employed quantitative reverse transcription PCR, immunohistochemistry, and differential expression analysis to investigate the association between GATA4 and inflammation-driven PDAC. We found that overexpression of GATA4 in pancreatic tumor tissue was accompanied by increased levels of inflammatory macrophages. We used macrophage-conditioned medium to validate inflammation models following treatment with varying concentrations of lipopolysaccharide and determined whether GATA4-dependent inflammatory stimuli affected pancreatic cancer cell invasion and growth in vitro. Nude mouse models of dibutyltin dichloride-induced chronic pancreatitis with orthotopic tumor xenografts were used to evaluate the effect of the inflammatory microenvironment on GATA4 expression in vivo. Our findings indicate that overexpression of GATA4 dramatically aggravated inflammatory stimuli-induced pancreatic cancer cell invasion and growth via NF-κB and STAT3 signaling, whereas silencing of GATA4 attenuated invasion and growth. Overall, our findings suggest that inflammation-driven cancer progression is dependent on GATA4 expression and is mediated through the STAT3 and NF-κB signaling pathways.

scholarly journals Effect of Adenomatous Polyposis Coli Loss on Tumorigenic Potential in Pancreatic Ductal Adenocarcinoma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1084 ◽  
Author(s):  
Jennifer M. Cole ◽  
Kaitlyn Simmons ◽  
Jenifer R. Prosperi
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Pancreatic Cancer Cell ◽  
Ductal Adenocarcinoma ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Pathway Activation ◽  
Functional Implications

Loss of the Adenomatous Polyposis Coli (APC) tumor suppressor in colorectal cancer elicits rapid signaling through the Wnt/β-catenin signaling pathway. In contrast to this well-established role of APC, recent studies from our laboratory demonstrated that APC functions through Wnt-independent pathways to mediate in vitro and in vivo models of breast tumorigenesis. Pancreatic ductal adenocarcinoma (PDAC) has an overall median survival of less than one year with a 5-year survival rate of 7.2%. APC is lost in a subset of pancreatic cancers, but the impact on Wnt signaling or tumor development is unclear. Given the lack of effective treatment strategies for pancreatic cancer, it is important to understand the functional implications of APC loss in pancreatic cancer cell lines. Therefore, the goal of this project is to study how APC loss affects Wnt pathway activation and in vitro tumor phenotypes. Using lentiviral shRNA, we successfully knocked down APC expression in six pancreatic cancer cell lines (AsPC-1, BxPC3, L3.6pl, HPAF-II, Hs 766T, MIA PaCa-2). No changes were observed in localization of β-catenin or reporter assays to assess β-catenin/TCF interaction. Despite this lack of Wnt/β-catenin pathway activation, the majority of APC knockdown cell lines exhibit an increase in cell proliferation. Cell migration assays showed that the BxPC-3 and L3.6pl cells were impacted by APC knockdown, showing faster wound healing in scratch wound assays. Interestingly, APC knockdown had no effect on gemcitabine treatment, which is the standard care for pancreatic cancer. It is important to understand the functional implications of APC loss in pancreatic cancer cells lines, which could be used as a target for therapeutics.

scholarly journals Inhibition of Sphingosine-1-Phosphate signaling in pancreatic ductal adenocarcinoma leads to downregulation of growth and invasion

2020 ◽  
Author(s):  
Brenna A. Rheinheimer ◽  
Alex Cardenas ◽  
Luis Camacho ◽  
Evan S. Ong ◽  
Tun Jie ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Leading Edge ◽  
Cancer Cell Lines ◽  
Ductal Adenocarcinoma ◽  
Sphingosine 1 Phosphate

AbstractBackgroundDeregulated phosphorylation of sphingosine by the sphingosine kinases and signaling through the EDG family of receptors enhances growth and survival in many cell types. Therefore, we sought to elucidate the effect of alterations in the ceramide/sphingosine/S1P rheostat on driving human pancreatic ductal adenocarcinoma towards a malignant phenotype.MethodsPancreatic cancer cell lines were treated with exogenous S1P, FTY720, and siRNA to Sphk1. Migration was evaluated by wound healing assays, cell growth by MTT assays, and invasion by tumorsphere assays. Expression of S1PR1, S1PR3, Sphk1, and Sphk2 were measured by quantitative PCR, western blot, and immunohistochemistry.ResultsS1PR1, S1PR3, and Sphk2 were overexpressed in all pancreatic cancer cell lines. Sphk1 translocated from the cytoplasm to the nucleus in cells located at the leading edge of cell clusters. Exogenous S1P increased cell migration while treatment with FTY720 and Sphk1 siRNA decreased cell growth and invasion.ConclusionsOur results suggest that increased S1PR1 expression may be an early event in pancreatic cancer pathogenesis. Additionally, altered Sphk1 localization may provide a mechanism through which pancreatic ductal adenocarcinoma cells at the leading edge invade into the surrounding matrix. Finally, inhibition of sphingosine-1-phosphate signaling may provide a novel therapeutic target for patients with metastatic disease.

DNAJA1 dysregulates metabolism promoting an anti-apoptotic phenotype in pancreatic ductal adenocarcinoma

2020 ◽  
Author(s):  
Heidi Roth ◽  
Fatema Bhinderwala ◽  
Rodrigo Franco ◽  
You Zhou ◽  
Robert Powers
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
The Impact

Abstract BackgroundAt less than 7%, pancreatic ductal adenocarcinoma (PDAC) has one of the poorest 5-year cancer survival rates and is set to be the leading cause of cancer related deaths by 2030. The co-chaperone protein DNAJA1 (HSP40) is downregulated four-fold in pancreatic cancer cells, but its impact on pancreatic ductal adenocarcinoma (PDAC) progression remains unclear.MethodsDNAJA1 was overexpressed in pancreatic cancer cell lines, BxPC-3 and MIA PaCa-2, through retroviral transfection. The impact of overexpressing DNAJA1 was investigated using a combination of untargeted metabolomics, stable isotope resolved metabolomics (SIRM), confocal microscopy, flow-cytometry, and cell-based assays.ResultsPancreatic cancer cells overexpressing DNAJA1 exhibited a global metabolomic change. Specifically, differential output from Warburg glycolysis, an increase in redox currency, and an alteration in amino acid levels were observed in both overexpression cell lines. DNAJA1 overexpression also led to mitochondrial fusion, an increase in the expression of Bcl-2, a modest protection from redox induced cell death, a loss of structural integrity due to the loss of actin fibers, and an increase in cell invasiveness in BxPC-3. These differences were more pronounced in BxPC-3, which contains a loss-of-function mutation in the tumor suppressing gene SMAD4.ConclusionsThe overexpression of DNAJA1 promoted cellular proliferation, redox tolerance, invasiveness, and anti-apoptosis, which suggests DNAJA1 has numerous regulatory roles. Overall, our findings suggest a proto-oncogenic role of DNAJA1 in PDAC progression and suggests DNAJA1 may function synergistically with other proteins with altered activity in pancreatic cancer cell lines.

Treatment of pancreatic ductal adenocarcinoma (PDAC) by argyrin F (AF) + gemcitabine (G).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 310-310
Author(s):  
Ruben R Plentz ◽  
Xi Chen ◽  
Samarpita Barat ◽  
Przemyslaw Bozko ◽  
Cuong Bui ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cell ◽  
Colony Formation ◽  
Pancreatic Cancer Cell ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Dependent Manner ◽  
Mesenchymal Transition

310 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of < 5%. Early diagnosis is rare and treatment options are often limited. Recent studies have reported that the proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. The aim of the present study is to explore the anti-tumor activity of this analogue Argyrin F (AF) + Gemcitabine (G) in PDAC carcinogenesis. Methods: We analyzed the effect of AF on proliferation and epithelial plasticity of different human pancreatic cancer cell lines by using MTT-, wound healing-, invasion-, colony formation-, apoptosis- and senescence assay, as well as cell cycle analysis and Western Blot. In vivo, we assessed the effects of AF and combinational (AF + G) therapy in a genetically engineered mouse model (Pdx1- Cre; LSL-KrasG12D; p53 lox/+) of PDAC. Results: AF inhibited pancreatic cancer cell proliferation, migration, invasion and colony formation compared to their respective untreated controls (DMSO). We also found that AF impairs epithelial-mesenchymal-transition (EMT) and induces considerable apoptosis and senescence in a dose-and time-dependent manner. AF application resulted in cell cycle G1/S phase transition. Most importantly, double treatment by AF + G showed prolonged survival and caused significant tumor reduction. Expression of Ki67 (anti-proliferative marker) and CD34 (tumor angiogenesis marker) was reduced both after AF and AF + G treatment of PDAC tumors in mice. Conclusions: Our work demonstrates that treatment with AF can successfully inhibit the growth of PDAC cells and combinational treatment with AF + G might be also a new and promising combinational therapy for human PDAC treatment.

scholarly journals FXYD3 is overexpressed in pancreatic ductal adenocarcinoma and influences pancreatic cancer cell growth

2005 ◽  
Vol 118 (1) ◽  
pp. 43-54 ◽  
Author(s):  
Hany Kayed ◽  
Jörg Kleeff ◽  
Armin Kolb ◽  
Knut Ketterer ◽  
Shereen Keleg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Ductal Adenocarcinoma ◽  
Cancer Cell Growth
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