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Find video protocols related to scientific articles indexed in Pubmed.
An angiopoietin-like protein 2 autocrine signaling promotes EMT during pancreatic ductal carcinogenesis.
Oncotarget
PUBLISHED: 06-26-2014
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The identification of the earliest molecular events responsible for the metastatic dissemination of pancreatic ductal adenocarcinoma (PDAC) remains critical for early detection, prevention, and treatment interventions. In this study, we hypothesized that an autocrine signaling between Angiopoietin-like Protein (ANGPTL)2 and its receptor leukocyte immunoglobulin-like receptor B2 (LILRB2) might be responsible for the epithelial-to-mesenchymal transition (EMT) and, the early metastatic behavior of cells in pancreatic preneoplastic lesions. We demonstrated that the sequential activation of KRAS, expression of HER2 and silencing of p16/p14 are sufficient to progressively and significantly increase the secretion of ANGPTL2, and the expression of LILRB2. Silencing the expression of ANGPTL2 reverted EMT and reduced migration in these cell lines. Blocking ANGPTL2 receptor LILRB2 in KRAS, and KRAS/HER2/p16p14shRNA LILRB2- expressing cells reduced ANGPTL2-induced cell proliferation and invasion. An increasingly significant overexpression of ANGPTL2 was observed in in a series of 68 different human PanIN and 27 PDAC lesions if compared with normal pancreatic parenchyma. These findings showed that the autocrine signaling of ANGPTL2 and its receptor LILRB2 plays key roles in sustaining EMT and the early metastatic behavior of cells in pancreatic preneoplastic lesions supporting the potential role of ANGPTL2 for early detection, metastasis prevention, and treatment in PDAC.
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SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium.
PLoS ONE
PUBLISHED: 01-01-2014
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Expression of the cellular adhesion protein N-cadherin is a critical event during epithelial-mesenchymal transition (EMT). The SMAD4 protein has been identified as a mediator of transforming growth factor-? (TGF-?) superfamily signaling, which regulates EMT, but the mechanisms linking TGF-? signaling to N-cadherin expression remain unclear. When the TGF-? pathway is activated, SMAD proteins, including the common mediator SMAD4, are subsequently translocated into the nucleus, where they influence gene transcription via SMAD binding elements (SBEs). Here we describe a mechanism for control of CDH2, the gene encoding N-cadherin, through the canonical TGF?-SMAD4 pathway. We first identified four previously undescribed SBEs within the CDH2 promoter. Using telomerase immortalized human pancreatic ductal epithelium, we found that TGF-? stimulation prompted specific SMAD4 binding to all four SBEs. Luciferase reporter and SMAD4-knockdown experiments demonstrated that specific SMAD4 binding to the SBE located at -3790 bp to -3795 bp within the promoter region of CDH2 was necessary for TGF-?-stimulated transcription. Expression of N-cadherin on the surface of epithelial cells facilitates motility and invasion, and we demonstrated that knockdown of SMAD4 causes decreased N-cadherin expression, which results in diminished migration and invasion of human pancreatic ductal epithelial cells. Similar reduction of cell motility was produced after CDH2 knockdown. Together, these findings suggest that SMAD4 is critical for the TGF-?-driven upregulation of N-cadherin and the resultant invasive phenotype of human pancreatic ductal epithelial cells during EMT.
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Cooperativity of oncogenic K-ras and downregulated p16/INK4A in human pancreatic tumorigenesis.
PLoS ONE
PUBLISHED: 01-01-2014
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Activation of K-ras and inactivation of p16 are the most frequently identified genetic alterations in human pancreatic epithelial adenocarcinoma (PDAC). Mouse models engineered with mutant K-ras and deleted p16 recapitulate key pathological features of PDAC. However, a human cell culture transformation model that recapitulates the human pancreatic molecular carcinogenesis is lacking. In this study, we investigated the role of p16 in hTERT-immortalized human pancreatic epithelial nestin-expressing (HPNE) cells expressing mutant K-ras (K-rasG12V). We found that expression of p16 was induced by oncogenic K-ras in these HPNE cells and that silencing of this induced p16 expression resulted in tumorigenic transformation and development of metastatic PDAC in an orthotopic xenograft mouse model. Our results revealed that PI3K/Akt, ERK1/2 pathways and TGF? signaling were activated by K-ras and involved in the malignant transformation of human pancreatic cells. Also, p38/MAPK pathway was involved in p16 up-regulation. Thus, our findings establish an experimental cell-based model for dissecting signaling pathways in the development of human PDAC. This model provides an important tool for studying the molecular basis of PDAC development and gaining insight into signaling mechanisms and potential new therapeutic targets for altered oncogenic signaling pathways in PDAC.
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Activation of the Transcription Factor c-Maf in T Cells Is Dependent on the CARMA1-IKK? Signaling Cascade.
Sci Signal
PUBLISHED: 12-19-2013
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The proto-oncogene c-Maf is a transcription factor that plays a critical role in the differentiation of various T helper (TH) cell subsets. The amount of c-Maf increases after stimulation of the T cell receptor (TCR), which results in the production of multiple cytokines. We showed that two essential regulators of the transcription factor nuclear factor ?B (NF-?B), the scaffold protein CARMA1 and the kinase IKK? [inhibitor of NF-?B (I?B) kinase ?], are also critical for the activation of c-Maf. Although CARMA1 deficiency did not affect the TCR-dependent increase in c-Maf abundance in T cells, CARMA1-dependent activation of the IKK complex was required for the nuclear translocation of c-Maf and its binding to the promoters of its target genes. Consistent with a role for c-Maf in the development of T follicular helper (TFH) cells, which provide help to B cells in the germinal centers of the spleen, CARMA1- or IKK?-deficient mice immunized with peptide antigen had defects in the generation of TFH cells, formation of germinal centers, and production of antigen-specific antibodies. Together, these data suggest a mechanism by which c-Maf is regulated during T cell activation and differentiation.
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Deciphering the mechanisms of tumorigenesis in human pancreatic ductal epithelial cells.
Clin. Cancer Res.
PUBLISHED: 01-22-2013
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The most common genetic lesions in pancreatic ductal adenocarcinoma (PDAC) have been identified. However, significant gaps still exist in our understanding of how such genetic alterations act in concert to induce PDAC development. In this study, we investigated the mechanism of tumorigenic transformation in the immortalized human pancreatic ductal epithelial (HPDE) cell line by sequentially introducing PDAC signature alterations into this cell line.
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A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer growth.
EMBO Mol Med
PUBLISHED: 01-15-2013
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Changes in the intracellular levels of the essential micronutrient zinc have been implicated in multiple diseases including pancreatic cancer; however, the molecular mechanism is poorly understood. Here, we report a novel mechanism where increased zinc mediated by the zinc importer ZIP4 transcriptionally induces miR-373 in pancreatic cancer to promote tumour growth. Reporter, expression and chromatin immunoprecipitation assays demonstrate that ZIP4 activates the zinc-dependent transcription factor CREB and requires this transcription factor to increase miR-373 expression through the regulation of its promoter. miR-373 induction is necessary for efficient ZIP4-dependent enhancement of cell proliferation, invasion, and tumour growth. Further analysis of miR-373 in vivo oncogenic function reveals that it is mediated through its negative regulation of TP53INP1, LATS2 and CD44. These results define a novel ZIP4-CREB-miR-373 signalling axis promoting pancreatic cancer growth, providing mechanistic insights explaining in part how a zinc transporter functions in cancer cells and may have broader implications as inappropriate regulation of intracellular zinc levels plays an important role in many other diseases.
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Oncogenic K-Ras and Loss of Smad4 Mediate Invasion by Activating an EGFR/NF-?B Axis That Induces Expression of MMP9 and uPA in Human Pancreas Progenitor Cells.
PLoS ONE
PUBLISHED: 01-01-2013
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Activating K-Ras mutations and inactivating mutations of Smad4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). To further study the individual and combinatorial roles of these two mutations in the pathogenesis of PDAC, immortalized human pancreas nestin postive cells (HPNE) were genetically modified by either expressing oncogenic K-Ras (HPNE/K-Ras), by shRNA knock down of Smad4 (HPNE/ShSmad4) or by creating both alterations in the same cell line (HPNE/K-Ras/ShSmad4). We previously found that expression of oncogenic K-Ras caused an increase in expression of EGFR and loss of Smad4 further enhanced the up regulation in expression of EGFR and that this increase in EGFR was sufficient to induce invasion. Here we further investigated the mechanism that links mutational alterations and EGFR expression with invasion. The increase in EGFR signaling was associated with up regulation of MMP9 and uPA protein and activity. Moreover, the increase in EGFR signaling promoted a nuclear translocation and binding of RelA (p65), a subunit of NF-?B, to the promoters of both MMP-9 and uPA. Treatment of HPNE/K-Ras/ShSmad4 cells with an inhibitor of EGFR reduced EGF-mediated NF-?B nuclear translocation and inhibitors of either EGFR or NF-?B reduced the increase in MMP-9 or uPA expression. In conclusion, this study provides the mechanism of how a combination of oncogenic K-Ras and loss of Smad4 causes invasion and provides the basis for new strategies to inhibit metastases.
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Kras, Pten, NF-?B, and inflammation: dangerous liaisons.
Cancer Discov
PUBLISHED: 11-06-2011
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Ying and colleagues identify a novel function of Pten as a haploinsufficient tumor suppressor in human pancreatic cancer development. Genomic, genetic, and biochemical data reveal that Pten loss and Kras mutation cooperate to accelerate pancreatic cancer development by altering PI3K regulation to enhance NF-?B activation and upregulate downstream cytokine genes; this provides a protumorigenic and metastatic microenvironment.
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K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis.
Cell Res.
PUBLISHED: 08-30-2011
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Increased aerobic glycolysis and oxidative stress are important features of cancer cell metabolism, but the underlying biochemical and molecular mechanisms remain elusive. Using a tetracycline inducible model, we show that activation of K-ras(G12V) causes mitochondrial dysfunction, leading to decreased respiration, elevated glycolysis, and increased generation of reactive oxygen species. The K-RAS protein is associated with mitochondria, and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore. Furthermore, pre-induction of K-ras(G12V) expression in vitro to allow metabolic adaptation to high glycolytic metabolism enhances the ability of the transformed cells to form tumor in vivo. Our study suggests that induction of mitochondrial dysfunction is an important mechanism by which K-ras(G12V) causes metabolic changes and ROS stress in cancer cells, and promotes tumor development.
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Modulation of pancreatic cancer chemoresistance by inhibition of TAK1.
J. Natl. Cancer Inst.
PUBLISHED: 07-08-2011
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TGF-?-activated kinase-1 (TAK1), a mitogen-activated protein kinase kinase kinase, functions in the activation of nuclear factor ?B (NF-?B) and activator protein-1, which can suppress proapoptotic signaling pathways and thus promote resistance to chemotherapeutic drugs. However, it is not known if inhibition of TAK1 is effective in reducing chemoresistance to therapeutic drugs against pancreatic cancer.
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Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype.
Clin. Cancer Res.
PUBLISHED: 07-07-2011
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The resistance of tumors to antiangiogenic therapies is becoming increasingly relevant. There are currently no validated predictive biomarkers for selecting which cancer patients will benefit from antiangiogenic therapy. Also lacking are resistance biomarkers that can identify which escape pathways should be targeted after tumors develop resistance to VEGF treatment. Recent studies showed that anti-VEGF treatment can make tumor cells more aggressive and metastatic. However, the mechanisms and mediators of this are unidentified. Therefore, we aimed this study at directly identifying the tumor cell-initiated mechanisms responsible for the resistance of pancreatic cancer to anti-VEGF treatment.
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Disruption of the NF-?B/I?B? Autoinhibitory Loop Improves Cognitive Performance and Promotes Hyperexcitability of Hippocampal Neurons.
Mol Neurodegener
PUBLISHED: 05-20-2011
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Though originally discovered in the immune system as an important mediator of inflammation, NF-?B has recently been shown to play key roles in the central nervous system, such as synaptogenesis, synaptic plasticity, and cognition. NF-?B activity is normally tightly regulated by its primary inhibitor, I?B?, through a unique autoinhibitory loop. In this study, we tested the hypothesis that the I?B? autoinhibitory loop ensures optimal levels of NF-?B activity to promote proper brain development and function. To do so, we utilized knock-in mice which possess mutations in the I?B? promoter to disrupt the autoinhibitory loop (I?B?M/M KI mice).
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The biphasic role of NF-kappaB in progression and chemoresistance of ovarian cancer.
Clin. Cancer Res.
PUBLISHED: 02-21-2011
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NF-?B is a transcription factor known to promote tumorigenesis. However, NF-?B is also known to be proapoptotic and may potentially function as a tumor suppressor, although such a functional role has not been extensively investigated in human cancer.
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Defective feedback regulation of NF-kappaB underlies Sjogrens syndrome in mice with mutated kappaB enhancers of the IkappaBalpha promoter.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-09-2010
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Feedback regulation of transcription factor NF-kappaB by its inhibitor IkappaBalpha plays an essential role in control of NF-kappaB activity. To understand the biological significance of IkappaBalpha-mediated feedback regulation of NF-kappaB, we generated mice harboring mutated kappaB enhancers in the promoter of the IkappaBalpha gene (IkappaBalpha(M/M)) to inhibit NF-kappaB-regulated IkappaBalpha expression. Here, we report that these mutant mice are defective in NF-kappaB-induced expression of IkappaBalpha. This defective feedback regulation of NF-kappaB by IkappaBalpha not only altered activity of NF-kappaB, but also the expression of NF-kappaB-regulated genes. As a result, IkappaBalpha(M/M), the homozygous knock-in mice with mutated kappaB enhancers in the IkappaBalpha promoter, acquire shorten life span, hypersensitivity to septic shock, abnormal T-cell development and activation, and Sjögrens Syndrome. These findings therefore demonstrate that the IkappaBalpha-mediated feedback regulation of NF-kappaB has an essential role in controlling T-cell development and functions, provide mechanistic insight into the development of Sjögrens Syndrome, and suggest the potential of NF-kappaB signaling as a therapeutic target for Sjögrens Syndrome and other autoimmune diseases.
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Doxycycline induces apoptosis in PANC-1 pancreatic cancer cells.
Anticancer Res.
PUBLISHED: 10-23-2009
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Tetracyclines such as doxycycline are reported to possess cytotoxic activity against mammalian tumor cells, but the mechanism of their effects on cell proliferation remains unclear.
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Oral poly(ADP-ribose) polymerase-1 inhibitor BSI-401 has antitumor activity and synergizes with oxaliplatin against pancreatic cancer, preventing acute neurotoxicity.
Clin. Cancer Res.
PUBLISHED: 10-06-2009
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Development of novel agents and drug combinations are urgently needed for treatment of pancreatic cancer. Oxaliplatin belongs to an important class of DNA-damaging organoplatinum agents, useful in pancreatic cancer therapy. However, increased ability of cancer cells to recognize and repair DNA damage enables resistance to these agents. Poly (ADP ribose) polymerase-1 is a sensor of DNA damage with key roles in DNA repair. Here, we report the therapeutic activity of the poly (ADP ribose) polymerase-1 inhibitor BSI-401, as a single agent and in combination with oxaliplatin in orthotopic nude mouse models of pancreatic cancer, and its effect on oxaliplatin-induced acute neurotoxicity.
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TrkBT1 induces liver metastasis of pancreatic cancer cells by sequestering Rho GDP dissociation inhibitor and promoting RhoA activation.
Cancer Res.
PUBLISHED: 09-22-2009
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Many genetic and molecular alterations, such as K-ras mutation and NF-kappaB activation, have been identified in pancreatic cancer. However, the mechanisms by which pancreatic cancer metastasizes still remain to be determined. Although we previously showed that the tropomyosin-related kinase B (TrkB) was significantly correlated with the development of liver metastasis, its function in pancreatic cancer metastasis remained unresolved. In the present study, we showed that overexpressed TrkB is an alternatively spliced transcript variant of TrkB (TrkBT1) with a unique COOH-terminal 12-amino acid sequence and is mainly localized in the cytoplasm. Our results showed that overexpression of Flag-tagged TrkBT1 but not a Flag-tagged TrkBT1 COOH-terminal deletion mutant (Flag-TrkBT1DeltaC) in nonmetastatic pancreatic cancer cells enhanced cell proliferation, promoted formation of colonies in soft agar, stimulated tumor cell invasion, and induced liver metastasis in an orthotopic xenograft mouse model of pancreatic cancer. TrkBT1 interacted with Rho GDP dissociation inhibitor (GDI) in vivo, but Flag-TrkBT1DeltaC did not. Furthermore, overexpression of Flag-TrkBT1 and knockdown of RhoGDI expression by RhoGDI short hairpin RNAs promoted RhoA activation, but Flag-TrkBT1DeltaC overexpression did not. Therefore, our results showed that TrkBT1 overexpression induces liver metastasis of pancreatic cancer and uncovered a unique signaling mechanism by which TrkBT1 sequesters GDI and activates RhoA signaling.
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Combination chemotherapy of nafamostat mesilate with gemcitabine for pancreatic cancer targeting NF-kappaB activation.
Anticancer Res.
PUBLISHED: 08-08-2009
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Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. However, chemoresistance to gemcitabine because of gemcitabine-induced nuclear factor-kappaB (NF-kappaB) activation has been reported. We previously reported that the synthetic serine protease inhibitor nafamostat mesilate inhibited NF-kappaB activation and induced apoptosis of pancreatic cancer cells. In this study, whether or not nafamostat mesilate could enhance the anticancer effect of gemcitabine was investigated.
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14-3-3zeta Cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelial-mesenchymal transition.
Cancer Cell
PUBLISHED: 05-20-2009
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ErbB2, a metastasis-promoting oncoprotein, is overexpressed in approximately 25% of invasive/metastatic breast cancers, but in 50%-60% of noninvasive ductal carcinomas in situ (DCIS). It has been puzzling how a subset of ErbB2-overexpressing DCIS develops into invasive breast cancer (IBC). We found that co-overexpression of 14-3-3zeta in ErbB2-overexpressing DCIS conferred a higher risk of progression to IBC. ErbB2 and 14-3-3zeta overexpression, respectively, increased cell migration and decreased cell adhesion, two prerequisites of tumor cell invasion. 14-3-3zeta overexpression reduced cell adhesion by activating the TGF-beta/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition. Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3zeta had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one.
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Secreted interleukin-1alpha induces a metastatic phenotype in pancreatic cancer by sustaining a constitutive activation of nuclear factor-kappaB.
Mol. Cancer Res.
PUBLISHED: 05-12-2009
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Transcription factor nuclear factor-kappaB (NF-kappaB) is constitutively activated in most pancreatic cancer tissues and cell lines but not in normal pancreas nor in immortalized/nontumorigenic human pancreatic ductal epithelial cells. Inhibition of constitutive NF-kappaB activation in pancreatic cancer cell lines suppresses tumorigenesis and tumor metastasis. Recently, we identified autocrine secretion of proinflammatory cytokine interleukin (IL)-1alpha as the mechanism of constitutive NF-kappaB activation in metastatic pancreatic cancer cell lines. However, the role of IL-1alpha in determining the metastatic potential of pancreatic tumor remains to be further investigated. In the current study, we stably expressed IL-1alpha in the nonmetastatic, IL-1alpha-negative MiaPaCa-2 cell lines. Our results showed that the secretion of IL-1alpha in MiaPaCa-2 cells constitutively activated NF-kappaB and increased the expression of NF-kappaB downstream genes involved in the different steps of the metastatic cascade, such as urokinase-type plasminogen activator, vascular endothelial growth factor, and IL-8. MiaPaCa-2/IL-1alpha cells showed an enhanced cell invasion in vitro compared with parental MiaPaCa-2 cells and induced liver metastasis in an orthotopic mouse model. The metastatic phenotype induced by IL-1alpha was inhibited by the expression of phosphorylation-defective IkappaB (IkappaB S32, 36A), which blocked NF-kappaB activation. Consistently, silencing the expression of IL-1alpha by short hairpin RNA in the highly metastatic L3.6pl pancreatic cancer cells completely suppressed their metastatic spread. In summary, these findings showed that IL-1alpha plays key roles in pancreatic cancer metastatic behavior through the constitutive activation of NF-kappaB. Our findings further support the possible link between inflammation and cancer and suggest that IL-1alpha may be a potential therapeutic target for treating pancreatic adenocarcinoma.
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Desensitization of NF?B for overcoming chemoresistance of pancreatic cancer cells to TNF-? or paclitaxel.
Anticancer Res.
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Chemotherapy-induced nuclear factor kappaB (NF?B) activation is thought to play a key role in acquisition of chemoresistance by cancer cells. We focused on blockade of this activation by using the observation so-called desensitization of NF?B using known NF?B activator, doxycycline.
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Study human pancreatic cancer in mice: how close are they?
Biochim. Biophys. Acta
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Pancreatic cancer is the fourth leading cause of cancer deaths and is characterized by dismal prognosis. Xenograft and genetically engineered mouse (GEM) models have recapitulated critical elements of human pancreatic cancer, providing useful tools to probe the underlying cause of cancer etiology. In this review, we provide a brief description of the common genetic lesions that occur during the development of pancreatic cancer. Next, we describe the strengths and weaknesses of these two models and highlight key discoveries each has made. Although the relative merits of GEM and xenograft pancreatic cancer mouse models are subject to debate, both systems have and will continue to yield essential insights in understanding pancreatic cancer etiology. This information is critical for the development of new methods to screen, treat, and prevent pancreatic cancer.
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EGFR-induced and PKC? monoubiquitylation-dependent NF-?B activation upregulates PKM2 expression and promotes tumorigenesis.
Mol. Cell
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Many types of human tumor cells have overexpressed pyruvate kinase M2 (PKM2). However, the mechanism underlying this increased PKM2 expression remains to be defined. We demonstrate here that EGFR activation induces PLC?1-dependent PKC? monoubiquitylation at Lys321 mediated by RINCK1 ubiquitin ligase. Monoubiquitylated PKC? interacts with a ubiquitin-binding domain in NEMO zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where PKC? phosphorylates IKK? at Ser177 and activates IKK?. Activated RelA interacts with HIF1?, which is required for RelA to bind the PKM promoter. PKC?- and NF-?B-dependent PKM2 upregulation is required for EGFR-promoted glycolysis and tumorigenesis. In addition, PKM2 expression correlates with EGFR and IKK? activity in human glioblastoma specimens and with grade of glioma malignancy. These findings highlight the distinct regulation of NF-?B by EGF, in contrast to TNF-?, and the importance of the metabolic cooperation between the EGFR and NF-?B pathways in PKM2 upregulation and tumorigenesis.
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KrasG12D-induced IKK2/?/NF-?B activation by IL-1? and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma.
Cancer Cell
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Constitutive Kras and NF-?B activation is identified as signature alterations in pancreatic ductal adenocarcinoma (PDAC). However, how NF-?B is activated in PDAC is not yet understood. Here, we report that pancreas-targeted IKK2/? inactivation inhibited NF-?B activation and PDAC development in Kras(G12D) and Kras(G12D);Ink4a/Arf(F/F) mice, demonstrating a mechanistic link between IKK2/? and Kras(G12D) in PDAC inception. Our findings reveal that Kras(G12D)-activated AP-1 induces IL-1?, which, in turn, activates NF-?B and its target genes IL-1? and p62, to initiate IL-1?/p62 feedforward loops for inducing and sustaining NF-?B activity. Furthermore, IL-1? overexpression correlates with Kras mutation, NF-?B activity, and poor survival in PDAC patients. Therefore, our findings demonstrate the mechanism by which IKK2/?/NF-?B is activated by Kras(G12D) through dual feedforward loops of IL-1?/p62.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.