NF-κB Dependent Chemokine Signaling in Pancreatic Cancer

Geismann, Claudia; Schäfer, Heiner; Gundlach, Jan-Paul; Hauser, Charlotte; Egberts, Jan‐Hendrik; Schneider, Günter; Arlt, Alexander

doi:10.3390/cancers11101445

Cited by 28 publications

(18 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, CLUSTER2 and 4, were mapped to the chemokine signaling pathway and type I interferon signaling pathway, respectively, and located close to each other in the PPI network. Although the importance of chemokine signaling in PDAC has been previously reported ( Geismann et al, 2019 ), the exact role of cellular innate antiviral response in the pathogenesis of PDAC remains elusive. In this study, OAS1, OAS2, and RSAD2, which play critical roles in cellular innate antiviral responses induced by type I and type II interferon, were found to be up-regulated in PDAC.…”

Section: Resultsmentioning

confidence: 99%

Integrated transcriptome meta-analysis of pancreatic ductal adenocarcinoma and matched adjacent pancreatic tissues

Atay

2020

PeerJ

View full text Add to dashboard Cite

A comprehensive meta-analysis of publicly available gene expression microarray data obtained from human-derived pancreatic ductal adenocarcinoma (PDAC) tissues and their histologically matched adjacent tissue samples was performed to provide diagnostic and prognostic biomarkers, and molecular targets for PDAC. An integrative meta-analysis of four submissions (GSE62452, GSE15471, GSE62165, and GSE56560) containing 105 eligible tumor-adjacent tissue pairs revealed 344 differentially over-expressed and 168 repressed genes in PDAC compared to the adjacent-to-tumor samples. The validation analysis using TCGA combined GTEx data confirmed 98.24% of the identified up-regulated and 73.88% of the down-regulated protein-coding genes in PDAC. Pathway enrichment analysis showed that “ECM-receptor interaction”, “PI3K-Akt signaling pathway”, and “focal adhesion” are the most enriched KEGG pathways in PDAC. Protein-protein interaction analysis identified FN1, TIMP1, and MSLN as the most highly ranked hub genes among the DEGs. Transcription factor enrichment analysis revealed that TCF7, CTNNB1, SMAD3, and JUN are significantly activated in PDAC, while SMAD7 is inhibited. The prognostic significance of the identified and validated differentially expressed genes in PDAC was evaluated via survival analysis of TCGA Pan-Cancer pancreatic ductal adenocarcinoma data. The identified candidate prognostic biomarkers were then validated in four external validation datasets (GSE21501, GSE50827, GSE57495, and GSE71729) to further improve reliability. A total of 28 up-regulated genes were found to be significantly correlated with worse overall survival in patients with PDAC. Twenty-one of the identified prognostic genes (ITGB6, LAMC2, KRT7, SERPINB5, IGF2BP3, IL1RN, MPZL2, SFTA2, MET, LAMA3, ARNTL2, SLC2A1, LAMB3, COL17A1, EPSTI1, IL1RAP, AK4, ANXA2, S100A16, KRT19, and GPRC5A) were also found to be significantly correlated with the pathological stages of the disease. The results of this study provided promising prognostic biomarkers that have the potential to differentiate PDAC from both healthy and adjacent-to-tumor pancreatic tissues. Several novel dysregulated genes merit further study as potentially promising candidates for the development of more effective treatment strategies for PDAC.

show abstract

Section: Resultsmentioning

confidence: 99%

Integrated transcriptome meta-analysis of pancreatic ductal adenocarcinoma and matched adjacent pancreatic tissues

Atay

2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…Intriguingly, both the PI3K/AKT and ERK 1/2 pathways induced by interactions between chemokines and their receptors can lead to nuclear factor kappa B (NF-κB) activation [97]. While the NF-κB pathway induces the upregulated expression of some chemokines such as CCL2, CCL5, CXCL5, CXCL8, CXCL10, CXCL12, and CX3CL1, it also participates in the antiapoptotic and proliferative effects of CCL5, CCL20, CXCL8, and CXCL12 in pancreatic cancer [98]. Importantly, chemokines can promote tumor cell survival by regulating the balance between NF-κB-associated pro-and antiapoptosis proteins.…”

Section: Roles Of Chemokines In Tumor Growth and Proliferationmentioning

confidence: 99%

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

Thu

Lee

Cho

2020

Cancers

167

131

View full text Add to dashboard Cite

Chemokines are chemotactic cytokines that mediate immune cell chemotaxis and lymphoid tissue development. Recent advances have indicated that chemokines and their cognate receptors play critical roles in cancer-related inflammation and cancer progression. On the basis of these findings, the chemokine system has become a new potential drug target for cancer immunotherapy. In this review, we summarize the essential roles of the complex network of chemokines and their receptors in cancer progression. Furthermore, we discuss the potential value of the chemokine system as a cancer prognostic marker. The chemokine system regulates the infiltration of immune cells into the tumor microenvironment, which induces both pro- and anti-immunity and promotes or suppresses tumor growth and proliferation, angiogenesis, and metastasis. Increasing evidence indicates the promising prognostic value of the chemokine system in cancer patients. While CCL2, CXCL10, and CX3CL1/CX3CR1 can serve as favorable or unfavorable prognostic factors depending on the cancer types, CCL14 and XCL1 possess good prognostic value. Other chemokines such as CXCL1, CXCL8, and CXCL12 are poor prognostic markers. Despite vast advances in our understanding of the complex nature of the chemokine system in tumor biology, knowledge about the multifaceted roles of the chemokine system in different types of cancers is still limited. Further studies are necessary to decipher distinct roles within the chemokine system in terms of cancer progression and to validate their potential value in cancer prognosis.

show abstract

“…A distinct characteristic of PDAC is its desmoplasia, consisting of a significant amount of cancer-associated fibroblasts (CAFs) and a very dense fibrotic stroma [51] [ Figure 2]. The CAFs are pro-inflammatory due to activation of several signaling factors including nuclear factor kappa B (NF-κB), signal transducer and activator of transcription (STAT)-1 and STAT-3, and transforming growth factor (TGF)-β/SMAD [51][52][53][54] . These signaling factors cooperate in active cross-talk with cancer cells through paracrine signaling factors including chemokines, insulin-like growth factor, and proteases [52][53][54][55][56] .…”

Section: Pcscsmentioning

confidence: 99%

“…The CAFs are pro-inflammatory due to activation of several signaling factors including nuclear factor kappa B (NF-κB), signal transducer and activator of transcription (STAT)-1 and STAT-3, and transforming growth factor (TGF)-β/SMAD [51][52][53][54] . These signaling factors cooperate in active cross-talk with cancer cells through paracrine signaling factors including chemokines, insulin-like growth factor, and proteases [52][53][54][55][56] . Furthermore, several pro-stemness paracrine factors are secreted by distinct CAFs [56][57][58][59][60][61][62] and support the self-renewal and the stemness properties of initial PCSCs in tumors or promote the conversion of cancer cells into PCSCs [63] .…”

Section: Pcscsmentioning

confidence: 99%

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Safa

2020

JCMT

View full text Add to dashboard Cite

Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). Tumor dissemination is associated with the activation of an epithelial-tomesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell-tocell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger the phenotypic transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs) or cancer-initiating cells in pancreatic tumors. PCSCs may represent sub-populations of tumor cells resistant to therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen as well as the drug transporter ABCG2 grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights a linkage between CSC and EMT. In this review, The current understanding of the PCSCs, signaling pathways regulating these cells, PDAC heterogeneity, EMT mechanism, and links between EMT and metastasis in PCSCs

show abstract

NF-κB Dependent Chemokine Signaling in Pancreatic Cancer

Cited by 28 publications

References 94 publications

Integrated transcriptome meta-analysis of pancreatic ductal adenocarcinoma and matched adjacent pancreatic tissues

Integrated transcriptome meta-analysis of pancreatic ductal adenocarcinoma and matched adjacent pancreatic tissues

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Contact Info

Product

Resources

About