scholarly journals Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells

Oncotarget ◽  
2015 ◽  
Vol 6 (8) ◽  
pp. 5772-5787 ◽  
Author(s):  
Srustidhar Das ◽  
Satyanarayana Rachagani ◽  
Maria P. Torres-Gonzalez ◽  
Imayavaramban Lakshmanan ◽  
Prabin D. Majhi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Terminal Domain ◽  
Pancreatic Cancer Cells ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal

scholarly journals A mechanical memory of pancreatic cancer cells

2019 ◽  
Author(s):  
Ilaria Carnevale ◽  
Mjriam Capula ◽  
Elisa Giovannetti ◽  
Thomas Schmidt ◽  
Stefano Coppola
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Traction Force ◽  
Long Term Memory ◽  
Mechanical Stimuli ◽  
Mechanical Adaptation ◽  
Pancreatic Cancer Cells ◽  
Mechanical Memory

Cells sense and respond to mechanical stimuli in healthy and pathological conditions. Although the major mechanisms un-derlying cellular mechanotransduction have been described, it remains largely unclear how cells store information on past mechanical cues over time. Such mechanical memory is extremely relevant in the onset of metastasis in which cancer cells migrate through tissues of different stiffness, e.g. from a stiffer tumor microenvironment to softer metastatic sites as commonly occurs for pancreatic cancer. Here, we used micropillar-based traction force microscopy to show that Suit-2.28 pancreatic cancer cells mechanically primed on a stiff matrix exerted higher traction forces even when transferred to a soft secondary matrix, as compared to soft-primed cells. This mechanical memory effect was mediated by the Yes-associated protein (YAP) and the microRNA-21 (miR-21) that are two mechanosensors initially identified as long-term memory keepers in mesenchymal stem cells. Soft-primed cells showed (i) a lower YAP nuclear translocation when transferred to a stiff secondary matrix and (ii) a loss of rigidity sensing through YAP, as compared to stiff-primed cells. The mechanical adaptation resulted in a differential expression of miR-21, inversely proportional to the priming rigidity. The long-term mechanical memory retained by miR-21 unveiled a previously unidentified mechanical modulation of drug resistance by past matrix stiffness. The higher expression of miR-21 in soft-primed cells correlated with the increased resistance to gemcitabine, as compared to stiff-primed and non-primed pancreatic cancer cells.

scholarly journals TGF-β downregulates PTEN via activation of NF-κB in pancreatic cancer cells

2010 ◽  
Vol 298 (2) ◽  
pp. G275-G282 ◽  
Author(s):  
Jimmy Y. C. Chow ◽  
Makiko Ban ◽  
Helen L. Wu ◽  
Flang Nguyen ◽  
Mei Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Dominant Negative ◽  
Boyden Chamber ◽  
Western Blots ◽  
Smad Signaling ◽  
Pancreatic Cancers ◽  
Pancreatic Cancer Cells

TGF-β utilizes receptor-activated SMAD signaling to mediate growth suppression; however, non-SMAD signaling that modulates the TGF-β response in epithelial cells become apparent when the SMAD signaling is abrogated, a common occurrence in pancreatic cancers. Here, we examined whether TGF-β utilized NF-κB to downregulate PTEN, a gene that is rarely mutated in pancreatic cancers. SMAD4-null BxPc3 and CAPAN-1 pancreatic cancer cells were treated with TGF-β (10 ng/ml) and lysed, and cellular proteins were analyzed by Western blots using p-IκB, p65, and PTEN antibodies. PTEN promoter and NF-κB activities were assessed by PTEN-luc and p-NF-luc constructs, respectively. Dominant negative p-IκB-α-M (NF-κB superrepressor) was used to block activation of NF-κB. Cell motility was assessed by Boyden chamber migration assay. TGF-β induced IκB-α phosphorylation followed by NF-κB p65 subunit nuclear translocation and increased NF-κB activity. IκB-α-M blocked TGF-β-induced NF-κB activity, reversed downregulated PTEN promoter activity and PTEN expression, and prevented augmentation of cell motility induced by TGF-β. SMAD4 restoration, but not knockdown of SMAD2 and/or 3, reversed TGF-β-induced NF-κB activity. Thus TGF-β suppresses PTEN in pancreatic cancer cells through NF-κB activation and enhances cell motility and invasiveness in a SMAD4-independent manner that can be counteracted when TGF-β-SMAD signaling is restored. The TGF-β/NF-κB/PTEN cascade may be a critical pathway for pancreatic cancer cells to proliferate and metastasize.

scholarly journals miR-33a suppresses the nuclear translocation of β-catenin to enhance gemcitabine sensitivity in human pancreatic cancer cells

Tumor Biology ◽  
2015 ◽  
Vol 36 (12) ◽  
pp. 9395-9403 ◽  
Author(s):  
Chen Liang ◽  
Zhen Wang ◽  
Ying-Yi Li ◽  
Bao-Hua Yu ◽  
Fei Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals Mutant p53 prevents GAPDH nuclear translocation in pancreatic cancer cells favoring glycolysis and 2-deoxyglucose sensitivity

2018 ◽  
Vol 1865 (12) ◽  
pp. 1914-1923 ◽  
Author(s):  
Giovanna Butera ◽  
Raffaella Pacchiana ◽  
Nidula Mullappilly ◽  
Marilena Margiotta ◽  
Stefano Bruno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Mutant P53 ◽  
Pancreatic Cancer Cells
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