scholarly journals MAZ-binding G4-decoy with locked nucleic acid and twisted intercalating nucleic acid modifications suppresses KRAS in pancreatic cancer cells and delays tumor growth in mice

2013 ◽  
Vol 41 (7) ◽  
pp. 4049-4064 ◽  
Author(s):  
Susanna Cogoi ◽  
Sonia Zorzet ◽  
Valentina Rapozzi ◽  
Imrich Géci ◽  
Erik B. Pedersen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Nucleic Acid ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Locked Nucleic Acid ◽  
Pancreatic Cancer Cells

scholarly journals TGF-βRII Knock-down in Pancreatic Cancer Cells Promotes Tumor Growth and Gemcitabine Resistance. Importance of STAT3 Phosphorylation on S727

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 254 ◽  
Author(s):  
Vincent Drubay ◽  
Nicolas Skrypek ◽  
Lucie Cordiez ◽  
Romain Vasseur ◽  
Céline Schulz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Locally Advanced ◽  
Western World ◽  
Pancreatic Cancer Cells ◽  
Stat3 Phosphorylation ◽  
The Impact

Pancreatic adenocarcinoma (PDAC) is one of the most deadly cancers in the Western world because of a lack of early diagnostic markers and efficient therapeutics. At the time of diagnosis, more than 80% of patients have metastasis or locally advanced cancer and are therefore not eligible for surgical resection. Pancreatic cancer cells also harbour a high resistance to chemotherapeutic drugs such as gemcitabine that is one of the main palliative treatments for PDAC. Proteins involved in TGF-β signaling pathway (SMAD4 or TGF-βRII) are frequently mutated in PDAC (50–80%). TGF-β signalling pathway plays antagonistic roles during carcinogenesis by initially inhibiting epithelial growth and later promoting the progression of advanced tumors and thus emerged as both tumor suppressor and oncogenic pathways. In order to decipher the role of TGF-β in pancreatic carcinogenesis and chemoresistance, we generated CAPAN-1 and CAPAN-2 cell lines knocked down for TGF-βRII (first actor of TGF-β signaling). The impact on biological properties of these TGF-βRII-KD cells was studied both in vitro and in vivo. We show that TGF-βRII silencing alters tumor growth and migration as well as resistance to gemcitabine. TGF-βRII silencing also leads to S727 STAT3 and S63 c-Jun phosphorylation, decrease of MRP3 and increase of MRP4 ABC transporter expression and induction of a partial EMT phenotype. These markers associated with TGF-β signaling pathways may thus appear as potent therapeutic tools to better treat/manage pancreatic cancer.

shRNA-MEDIATED KNOCKDOWN OF CCK mRNA IN PANCREATIC CANCER CELLS DOES NOT ALTER IN VIVO TUMOR GROWTH

Pancreas ◽  
2008 ◽  
Vol 37 (4) ◽  
pp. 484
Author(s):  
G. Matters ◽  
C. McGovern ◽  
J. Harms ◽  
K. Markovic ◽  
K. Anson ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells

scholarly journals Expression of core 3 synthase in human pancreatic cancer cells suppresses tumor growth and metastasis

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Prakash Radhakrishnan ◽  
Paul M. Grandgenett ◽  
Ashley M. Mohr ◽  
Stephanie K. Bunt ◽  
Fang Yu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Tumor Growth And Metastasis

scholarly journals Modulation of the Leptin Receptor Mediates Tumor Growth and Migration of Pancreatic Cancer Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0126686 ◽  
Author(s):  
Alisha M. Mendonsa ◽  
Madeleine C. Chalfant ◽  
Lee D. Gorden ◽  
Michael N. VanSaun
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Leptin Receptor ◽  
Pancreatic Cancer Cells ◽  
And Migration

scholarly journals Novel Compound C150 Inhibits Pancreatic Cancer Cell Epithelial-to-Mesenchymal Transition and Tumor Growth in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Wang ◽  
Ping Chen ◽  
Ruochen Dong ◽  
Scott Weir ◽  
Michael Baltezor ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Epithelial To Mesenchymal Transition ◽  
Pancreatic Cancer Cell ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

Pancreatic cancer cell epithelial-to-mesenchymal transition (EMT) is an important contributor to cell invasion and tumor progression. Therefore, targeting EMT may be beneficial for pancreatic cancer treatment. The aim of the present study was to report on the inhibitory effect of the novel compound C150 on the EMT of pancreatic cancer cells. C150 inhibited cell proliferation in multiple pancreatic cancer cells with IC50 values of 1-2.5 μM, while in an non-cancerous pancreatic epithelial cell line hTERT-HPNE the IC50 value was >12.5 μM. C150 significantly inhibited pancreatic cancer cell migration and invasion, as demonstrated by 3-dimensional cell invasion, wound healing and Boyden chamber Transwell migration-invasion assays. Moreover, C150 treatment decreased MMP-2 gene expression in PANC-1 cells and reduced MMP-2 activity in gelatin zymography assay. In an orthotopic mouse model of pancreatic cancer, C150 significantly reduced tumor growth at the dose of 15 mg/kg by intraperitoneal injection three times per week. Furthermore, C150 enhanced protein degradation of Snail, an important EMT-promoting transcription factor, and decreased the expression of the mesenchymal marker N-cadherin, while it increased the expression of the epithelial markers zonula occludens-1 and claudin-1. The findings of the present study suggested that C150 is a novel EMT inhibitor that may be promising for inhibiting pancreatic cancer growth and metastasis.

scholarly journals Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1

2020 ◽  
Author(s):  
Pei-Yun Tsai ◽  
Min-Sik Lee ◽  
Unmesh Jadhav ◽  
Insia Naqvi ◽  
Shariq Madha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Glutamine Synthetase ◽  
Tumor Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Ductal Adenocarcinoma ◽  
Nutrient Deprivation ◽  
Open Chromatin ◽  
Nucleotide Synthesis ◽  
Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDA) is a lethal, therapy-resistant cancer that thrives in a highly desmoplastic, nutrient-deprived microenvironment. Several studies investigated the effects of depriving PDA of either glucose or glutamine alone. However, the consequences on PDA growth and metabolism of limiting both preferred nutrients have remained largely unknown. Here, we report the selection for clonal human PDA cells that survive and adapt to limiting levels of both glucose and glutamine. We find that adapted clones exhibit increased growth in vitro and enhanced tumor-forming capacity in vivo. Mechanistically, adapted clones share common transcriptional and metabolic programs, including amino acid use for de novo glutamine and nucleotide synthesis. They also display enhanced mTORC1 activity that prevents the proteasomal degradation of glutamine synthetase (GS), the rate-limiting enzyme for glutamine synthesis. This phenotype is notably reversible, with PDA cells acquiring alterations in open chromatin upon adaptation. Silencing of GS suppresses the enhanced growth of adapted cells and mitigates tumor growth. These findings identify non-genetic adaptations to nutrient deprivation in PDA and highlight GS as a dependency that could be targeted therapeutically in pancreatic cancer patients.SignificancePancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with no effective therapies. PDA aggressiveness partly stems from its ability to grow within a uniquely dense stroma restricting nutrient access. This study demonstrates that PDA clones that survive chronic nutrient deprivation acquire reversible non-genetic adaptations allowing them to switch between metabolic states optimal for growth under nutrient-replete or nutrient-deprived conditions. One contributing factor to this adaptation mTORC1 activation, which stabilizes glutamine synthetase (GS) necessary for glutamine generation in nutrient-deprived cancer cells. Our findings imply that although total GS levels may not be a prognostic marker for aggressive disease, GS inhibition is of high therapeutic value, as it targets specific cell clusters adapted to nutrient starvation, thus mitigating tumor growth.

scholarly journals Long noncoding RNA SOX2OT promotes pancreatic cancer cell migration and invasion through destabilizing FUS protein via ubiquitination

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Wang ◽  
Xiong-Fei Zhang ◽  
Dong-Yan Wang ◽  
Yi Zhu ◽  
Lei Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Migration ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Migration ◽  
Pancreatic Cancer Cells ◽  
Tumor Growth And Metastasis ◽  
Fus Protein

AbstractPancreatic cancer is a highly aggressive and lethal digestive system malignancy. Our previous studies revealed the correlation of high levels of lncRNA SOX2OT expression with patients’ poor survival outcomes, the promoting role of SOX2OT in proliferation and cycle progression of pancreatic cancer cells, and the in vivo binding of SOX2OT to RNA binding protein FUS, which destabilized the protein expression of FUS. However, the mechanism of SOX2OT binding and inhibiting FUS protein stability remains unclear. In this study, we performed RNA pull-down, cycloheximide-chase, and ubiquitination assays to determine the effect of SOX2OT on FUS ubiquitination, and explored the specific regulatory mechanism of SOX2OT–FUS axis in pancreatic cancer cell migration, invasion, in vivo tumor growth, and metastasis through RNA sequencing. We found that SOX2OT binds to FUS through its 5′ and 3′ regions, resulting in FUS ubiquitination and degradation. The SOX2OT–FUS regulatory axis promotes migration, invasion, tumor growth, and metastasis ability of pancreatic cancer cells. The in-depth elaboration of the SOX2OT–FUS regulatory axis in pancreatic cancer may clarify the mechanism of action of SOX2OT and provide new ideas for pancreatic cancer treatment.

Abstract 299: Modulation of the leptin receptor in pancreatic cancer cells mediates tumor growth

2012 ◽  
Author(s):  
Alisha Mendonsa ◽  
Madeleine Chalfant ◽  
Nagaraj Nagathihalli ◽  
Nipun Merchant ◽  
Lee Gorden ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Leptin Receptor ◽  
Pancreatic Cancer Cells
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