Mitogen-activated protein kinases(MAPK) and nuclear factor kappa B(NF-κB) pathways are considered to be two crucial intracellular signaling cascades in pro-inflammatory responses.In this study,we reported the coding ...Mitogen-activated protein kinases(MAPK) and nuclear factor kappa B(NF-κB) pathways are considered to be two crucial intracellular signaling cascades in pro-inflammatory responses.In this study,we reported the coding sequences(CDS) of MAPKp38 and NF-κBp65 from yellow catfish.We also investigated the gene structure,expression patterns and functional role in yellow catfish.The CDS of MAPKp38 is1,086 bp encoding 361 amino acids(AA).The MAPKp38 protein has a long highly conserved serine/threonine protein kinases catalytic domain.The NF-κBp65 CDS is 1,794 bp,and the gene encodes 597 AA,with a Rel homology domain(RHD) which consists of a RHD-DNA-binding domain and an Ig-like,plexins,transcription factors(IPT) domain.Moreover,MAPKp38 and NF-κBp65 protein of bony fish and other vertebrates have a single clade.Quantitative real-time PCR analysis revealed the presence of the MAPKp38 and NF-κBp65 transcript in 12 tissues of healthy yellow catfish.The highest expression levels of MAPKp38 and NF-κBp65 were detected in the heart and liver,respectively.Upon stimulation with an intraperitoneal injection of lipopolysaccharide(LPS),the expression levels of MAPKp38 and NF-κBp65 were up-regulated in the intestine.These results indicated that MAPKp38 and NF-κBp65 play important roles in mediating the response protection against LPS in yellow catfish.展开更多
Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely unde...Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein(PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration;this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B(NF-κB)signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3(FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29(SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated,and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.展开更多
Pancreatic cancer is ranked as the fourth leading cause of cancer-related mortality and is predicted to become the second leading cause of cancer-related death by 2030.The cause of this high mortality rate is due to p...Pancreatic cancer is ranked as the fourth leading cause of cancer-related mortality and is predicted to become the second leading cause of cancer-related death by 2030.The cause of this high mortality rate is due to pancreatic ductal adenocarcinoma’s rapid progression and metastasis,and development of drug resistance.Today,cancer immunotherapy is becoming a strong candidate to not only treat various cancers but also to combat against chemoresistance.Studies have suggested that complement system pathways play an important role in cancer progression and chemoresistance,especially in pancreatic cancer.A recent report also suggested that several signaling pathways play an important role in causing chemoresistance in pancreatic cancer,major ones including nuclear factor kappa B,signal transducer and activator of transcription 3,c-mesenchymal-epithelial transition factor,and phosphoinositide-3-kinase/protein kinase B.In addition,it has also been proven that the complement system has a very active role in establishing the tumor microenvironment,which would aid in promoting tumorigenesis,progression,metastasis,and recurrence.Interestingly,it has been shown that the downstream products of the complement system directly upregulate inflammatory mediators,which in turn activate these chemo-resistant pathways.Therefore,targeting complement pathways could be an innovative approach to combat against pancreatic cancer drugs resistance.In this review,we have discussed the role of complement system pathways in pancreatic cancer drug resistance and a special focus on the complement as a therapeutic target in pancreatic cancer.展开更多
基金financially supported by the National Natural Science Foundation of China (31702362)the Applied Basic Research Programs of Science and Technology Commission Foundation of Sichuan Province,China (grant number 2015JY0067).
文摘Mitogen-activated protein kinases(MAPK) and nuclear factor kappa B(NF-κB) pathways are considered to be two crucial intracellular signaling cascades in pro-inflammatory responses.In this study,we reported the coding sequences(CDS) of MAPKp38 and NF-κBp65 from yellow catfish.We also investigated the gene structure,expression patterns and functional role in yellow catfish.The CDS of MAPKp38 is1,086 bp encoding 361 amino acids(AA).The MAPKp38 protein has a long highly conserved serine/threonine protein kinases catalytic domain.The NF-κBp65 CDS is 1,794 bp,and the gene encodes 597 AA,with a Rel homology domain(RHD) which consists of a RHD-DNA-binding domain and an Ig-like,plexins,transcription factors(IPT) domain.Moreover,MAPKp38 and NF-κBp65 protein of bony fish and other vertebrates have a single clade.Quantitative real-time PCR analysis revealed the presence of the MAPKp38 and NF-κBp65 transcript in 12 tissues of healthy yellow catfish.The highest expression levels of MAPKp38 and NF-κBp65 were detected in the heart and liver,respectively.Upon stimulation with an intraperitoneal injection of lipopolysaccharide(LPS),the expression levels of MAPKp38 and NF-κBp65 were up-regulated in the intestine.These results indicated that MAPKp38 and NF-κBp65 play important roles in mediating the response protection against LPS in yellow catfish.
基金supported by grants from the National Science Foundation of China (31670170 & 81560442)from MOST (2018YFA0507201)from the Natural Science Foundation of Guangdong Province (2017ZC0236)。
文摘Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein(PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration;this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B(NF-κB)signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3(FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29(SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated,and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.
文摘Pancreatic cancer is ranked as the fourth leading cause of cancer-related mortality and is predicted to become the second leading cause of cancer-related death by 2030.The cause of this high mortality rate is due to pancreatic ductal adenocarcinoma’s rapid progression and metastasis,and development of drug resistance.Today,cancer immunotherapy is becoming a strong candidate to not only treat various cancers but also to combat against chemoresistance.Studies have suggested that complement system pathways play an important role in cancer progression and chemoresistance,especially in pancreatic cancer.A recent report also suggested that several signaling pathways play an important role in causing chemoresistance in pancreatic cancer,major ones including nuclear factor kappa B,signal transducer and activator of transcription 3,c-mesenchymal-epithelial transition factor,and phosphoinositide-3-kinase/protein kinase B.In addition,it has also been proven that the complement system has a very active role in establishing the tumor microenvironment,which would aid in promoting tumorigenesis,progression,metastasis,and recurrence.Interestingly,it has been shown that the downstream products of the complement system directly upregulate inflammatory mediators,which in turn activate these chemo-resistant pathways.Therefore,targeting complement pathways could be an innovative approach to combat against pancreatic cancer drugs resistance.In this review,we have discussed the role of complement system pathways in pancreatic cancer drug resistance and a special focus on the complement as a therapeutic target in pancreatic cancer.
