Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-tumor tissue derived interleukin-17B activates IL-17RB/AKT/β-catenin pathway to enhance the stemness of gastric cancer.

ABSTRACT: Inflammation is a critical component involved in tumor progression. Interleukin-17 (IL-17) belongs to a relatively new family of cytokines that has been associated with the progression of cancers. However, the role of IL-17B/IL-17RB (IL-17 receptor B) signaling to stemness of gastric cancer remains unknown. Here, we confirmed that the expression of IL-17RB in gastric cancer tissues was significantly increased, that overexpression was associated with poor prognosis of gastric cancer patients, and that overexpression was positively correlated with some stemness markers. Interestingly, the expression of IL-17B was upregulated in patient serum rather than gastric tumor tissues. Furthermore, exogenous rIL-17B significantly promoted the stemness of gastric cancer cells depending on IL-17RB and induced the expression of IL-17RB. Simultaneously, the expression of phosphorylated AKT, GSK-3β, and β-catenin as well as the nuclear translocation of β-catenin were significantly increased in the MGC-803 cell in a dose-dependent manner, when treated with rIL-17B. The AKT inhibitor, LY294002, and the knockdown of AKT expression reversed the rIL-17B-induced upregulation of β-catenin and some stemness markers. Together, our results indicate that the IL-17B/IL-17RB signal can promote the growth and migration of tumor cells, and upregulate cell stemness through activating the AKT/β-catenin pathway in gastric cancer, suggesting that IL-17RB may be a novel target in human gastric cancer therapy.

SUBMITTER: Bie Q

PROVIDER: S-EPMC4857095 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The Emerging Role of the IL-17B/IL-17RB Pathway in Cancer.

Project description:Among inflammatory mediators, a growing body of evidence emphasizes the contribution of the interleukin 17 (IL-17) cytokine family in malignant diseases. Besides IL-17A, the prototypic member of the IL-17 family, several experimental findings strongly support the role of the IL-17B/IL-17 receptor B (IL-17RB) pathway in tumorigenesis and resistance to anticancer therapies. In mouse models, IL-17B signaling through IL-17RB directly promotes cancer cell survival, proliferation, and migration, and induces resistance to conventional chemotherapeutic agents. Importantly, recent work by our and other laboratories showed that IL-17B signaling dramatically alters the tumor microenvironment by promoting chemokine and cytokine secretion which foster tumor progression. Moreover, the finding that elevated IL-17B is associated with poor prognosis in patients with pancreatic, gastric, lung, and breast cancer strengthens the results obtained in pre-clinical studies and highlights its clinical relevance. Here, we review the current understanding on the IL-17B/IL-17RB expression patterns and biological activities in cancer and highlight issues that remain to be addressed to better characterize IL-17B and its receptor as potential targets for enhancing the effectiveness of the existing cancer therapies.

| S-EPMC7186465 | biostudies-literature

Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines.

Project description:Pancreatic cancer has an extremely high mortality rate due to its aggressive metastatic nature. Resolving the underlying mechanisms will be crucial for treatment. Here, we found that overexpression of IL-17B receptor (IL-17RB) strongly correlated with postoperative metastasis and inversely correlated with progression-free survival in pancreatic cancer patients. Consistently, results from ex vivo experiments further validated that IL-17RB and its ligand, IL-17B, plays an essential role in pancreatic cancer metastasis and malignancy. Signals from IL-17B-IL-17RB activated CCL20/CXCL1/IL-8/TFF1 chemokine expressions via the ERK1/2 pathway to promote cancer cell invasion, macrophage and endothelial cell recruitment at primary sites, and cancer cell survival at distant organs. Treatment with a newly derived monoclonal antibody against IL-17RB blocked tumor metastasis and promoted survival in a mouse xenograft model. These findings not only illustrate a key mechanism underlying the highly aggressive characteristics of pancreatic cancer but also provide a practical approach to tackle this disease.

| S-EPMC4354366 | biostudies-literature

IL-17B activated mesenchymal stem cells enhance proliferation and migration of gastric cancer cells.

Project description:Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors. In addition, rIL-17B also activated the NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells.

| S-EPMC5386657 | biostudies-literature

IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination.

Project description:Cancer stem cells (CSCs) are characterized by robust self-renewal and tumorigenesis and are responsible for metastasis, drug resistance, and angiogenesis. However, the molecular mechanisms for the regulation of CSC homeostasis are incompletely understood. This study demonstrated that the interleukin-17 (IL-17)B/IL-17RB signaling cascade promotes the self-renewal and tumorigenesis of CSCs by inducing Beclin-1 ubiquitination. We found that IL-17RB expression was significantly upregulated in spheroid cells and Lgr5-positive cells from the same tumor tissues of patients with gastric cancer (GC), which was closely correlated with the degree of cancer cell differentiation. Recombinant IL-17B (rIL-17B) promoted the sphere-formation ability of CSCs in vitro and enhanced tumor growth and metastasis in vivo. Interestingly, IL-17B induced autophagosome formation and cleavage-mediated transformation of LC3 in CSCs and 293T cells. Furthermore, inhibition of autophagy activation by ATG7 knockdown reversed rIL-17B-induced self-renewal of GC cells. In addition, we showed that IL-17B also promoted K63-mediated ubiquitination of Beclin-1 by mediating the binding of tumor necrosis factor receptor-associated factor 6 to Beclin-1. Silencing IL-17RB expression abrogated the effects of IL-17B on Beclin-1 ubiquitination and autophagy activation in GC cells. Finally, we showed that IL-17B level in the serum of GC patients was positively correlated with IL-17RB expression in GC tissues, and IL-17B could induce IL-17RB expression in GC cells. Overall, the results elucidate the novel functions of IL-17B for CSCs and suggest that the intervention of the IL-17B/IL-17RB signaling pathway may provide new therapeutic targets for the treatment of cancer.

| S-EPMC7994204 | biostudies-literature

Anti-cancer drug 3,3'-diindolylmethane activates Wnt4 signaling to enhance gastric cancer cell stemness and tumorigenesis.

Project description:As a natural health supplement, 3,3'-diindolylmethane (DIM) is proposed as a preventive and chemotherapeutic agent for cancer by inhibiting cell proliferation and inducing cell apoptosis. However, we found that in contrary to high level of DIM (30 ?M), low level of DIM (1 ?M and 10 ?M) obviously promoted gastric cancer cell growth and migration. In addition, we found that low level of DIM increased the expression of stemness factors and enhanced the pluripotency of gastric cancer cells. Low level of DIM promoted gastric cancer progression by inducing the PORCN-dependent secretion of Wnt4 and the activation of ?-catenin signaling. Wnt4 knockdown reversed the effects of low level of DIM on gastric cancer cells. The results of in vivo studies showed that gastric cancer cells treated with low level of DIM (1 ?M) grew faster and expressed higher level of Wnt4 than control cells. Taken together, our findings indicate that low level of DIM activates autocrine Wnt4 signaling to enhance the progression of gastric cancer, which may suggest an adverse aspect of DIM in cancer therapy. Our findings will provide a new aspect for the safety of DIM in its clinical application.

| S-EPMC4941316 | biostudies-other

Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation.

Project description:The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in inflammatory diseases. Among them, IL-25 has been shown to be important in allergic inflammation and protection against parasitic infection. Here we have demonstrated that IL-17B, a poorly understood cytokine, functions to inhibit IL-25-driven inflammation. IL-17B and IL-25, both binding to the interleukin-17 receptor B (IL-17RB), were upregulated in their expression after acute colonic inflammation. Individual inhibition of these cytokines revealed opposing functions in colon inflammation: IL-25 was pathogenic but IL-17B was protective. Similarly opposing phenotypes were observed in Citrobacter rodentium infection and allergic asthma. Moreover, IL-25 was found to promote IL-6 production from colon epithelial cells, which was inhibited by IL-17B. Therefore, our data demonstrate that IL-17B is an anti-inflammatory cytokine in the IL-17 family.

| S-EPMC5811222 | biostudies-literature

IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination

Project description:Recombinant IL-17B (rIL-17B) promoted the sphere formation ability of CSCs in vitro and enhanced tumor growth and metastasis in vivo. Furthermore, the activation of autophagy was critically involved in IL-17B/IL-17RB-mediated regulation of CSC functions.

2022-01-28 | GSE164038 | GEO

TNFRSF11B activates Wnt/?-catenin signaling and promotes gastric cancer progression.

Project description:Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) has been studied to be involved in the development and progression of several human malignancies. However, little is unveiled regarding the complex mechanisms of TNFRSF11B in human gastric cancer (GC). The clinical significance of TNFRSF11B was assessed in 70 and 160 GC tissues using immunohistochemistry method and gene microarray analysis, respectively. The biological function of TNFRSF11B was studied in vitro and in vivo assays. Immunofluorescence assay was used to evaluate the expression of ?-catenin in the nucleus. The expression of ?-catenin and related protein was determined by Western blot. The interaction between TNFRSF11B and GSK3? was detected by co-immunoprecipitation. We demonstrated that TNFRSF11B was highly expressed in the cytoplasm of GC and associated with the patient poor outcome. Our studies showed that TNFRSF11B in GC cells significantly promoted cell proliferation, migration, invasion in vitro and tumorigenic ability in vitro and in vivo. Meanwhile, TNFRSF11B inhibited GC cell apoptosis. The proportion of nuclear active ?-catenin showed positively correlation with TNFRSF11B expression. TNFRSF11B directly combined with GSK-3? upregulating its phosphorylation, and increased expression of ?-catenin and its downstream effectors. Collectively, these findings demonstrate that TNFRSF11B promote the aggressive phenotypes of GC cells and activated Wnt/?-catenin signaling. Accordingly, TNFRSF11B had potential as a biomarker and inhibition of TNFRSF11B expression might offer a new therapeutic target for GC patients.

| S-EPMC7211174 | biostudies-literature

let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis.

Project description:BACKGROUND: Aberrant AKT activation contributes to gastric cancer cell survival and chemotherapy resistance, however its regulation is poorly understood. microRNAs have been established to be important regulators in gastric carcinogenesis. Here, we showed the functional role and putative target of let-7b and let-7g (let-7b/g) in gastric carcinogenesis. METHODS: The expression of let-7b/g in gastric cancer cell lines and primary tumors were evaluated by miRNA qRT-PCR. The putative target gene of let-7b/g was explored by TargetScan followed by further validation. Functional analyses including MTT proliferation, monolayer colony formation, cell invasion assays and in vivo study were performed in both ectopic expression and knockdown approaches. RESULTS: let-7b/g was found down-regulated in gastric cancer and its downregulation was associated with poor survival and correlated with lymph node metastasis. let-7b/g inhibited AKT2 expression by directly binding to its 3'UTR, reduced p-AKT (S473) activation and suppressed expression of the downstream effector pS6. AKT2 mRNA expression showed negative correlation with the expression of let-7b/g in primary tumors. Short interfering RNA (siRNA) mediated knockdown of AKT2 phenocopied the tumor-suppressive effects of let-7b/g. Moreover, AKT2 re-expression partly abrogated the growth-inhibitory effect of let-7b/g. CONCLUSION: In conclusion, our findings reveal decreased let-7b/g contributes to aberrant AKT activation in gastric tumorigenesis and provide a potential therapeutic strategy for gastric cancer.

| S-EPMC4196013 | biostudies-literature

Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family.

Project description:IL-17 is a T cell-derived cytokine that may play an important role in the initiation or maintenance of the proinflammatory response. Whereas expression of IL-17 is restricted to activated T cells, the IL-17 receptor is found to be widely expressed, a finding consistent with the pleiotropic activities of IL-17. We have cloned and expressed two novel human cytokines, IL-17B and IL-17C, that are related to IL-17 ( approximately 27% amino acid identity). IL-17B mRNA is expressed in adult pancreas, small intestine, and stomach, whereas IL-17C mRNA is not detected by RNA blot hybridization of several adult tissues. No expression of IL-17B or IL-17C mRNA is found in activated T cells. In a survey of cytokine induction, IL-17B and IL-17C stimulate the release of tumor necrosis factor alpha and IL-1beta from the monocytic cell line, THP-1, whereas IL-17 has only a weak effect in this system. No induction of IL-1alpha, IL-6, IFN-gamma, or granulocyte colony-stimulating factor is found in THP-1 cells. Fluorescence-activated cell sorter analysis shows that IL-17B and IL-17C bind to THP-1 cells. Conversely, IL-17B and IL-17C are not active in an IL-17 assay or the stimulation of IL-6 release from human fibroblasts and do not bind to the human IL-17 receptor extracellular domain. These data show that there is a family of IL-17-related cytokines differing in patterns of expression and proinflammatory responses that may be transduced through a cognate set of cell surface receptors.

| S-EPMC15406 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data