Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Wnt/beta-catenin signaling in T-cell immunity and cancer immunotherapy.

ABSTRACT: Wnt ligands are lipid-modified secreted glycoproteins that regulate embryonic development, cell fate specification, and the homeostasis of self-renewing adult tissues. In addition to its well-established role in thymocyte development, recent studies have indicated that Wnt/?-catenin signaling is critical for the differentiation, polarization, and survival of mature T lymphocytes. Here, we describe our current understanding of Wnt signaling in the biology of post-thymic T cells, and discuss how harnessing the Wnt/?-catenin pathway might improve the efficacy of vaccines, T-cell-based therapies, and allogeneic stem cell transplantation for the treatment of patients with cancer.

SUBMITTER: Gattinoni L

PROVIDER: S-EPMC3393131 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Wnt/beta-catenin signaling in T-cell immunity and cancer immunotherapy.

Gattinoni Luca L Ji Yun Y Restifo Nicholas P NP

Clinical cancer research : an official journal of the American Association for Cancer Research 20100805 19

Wnt ligands are lipid-modified secreted glycoproteins that regulate embryonic development, cell fate specification, and the homeostasis of self-renewing adult tissues. In addition to its well-established role in thymocyte development, recent studies have indicated that Wnt/β-catenin signaling is critical for the differentiation, polarization, and survival of mature T lymphocytes. Here, we describe our current understanding of Wnt signaling in the biology of post-thymic T cells, and discuss how h ...[more]

PMID: 20688898

Similar Datasets

Wnt2 complements Wnt/β-catenin signaling in colorectal cancer.

Project description:Wnt2 is implicated in various human cancers. However, it remains unknown how Wnt2 is upregulated in human cancer and contributes to tumorigenesis. Here we found that Wnt2 is highly expressed in colorectal cancer (CRC) cells. In addition to co-expression of Wnt2 with Wnt/β-catenin target genes in CRC, knockdown or knockout of Wnt2 significantly downregulates Wnt/β-catenin target gene expression in CRC cells. Importantly, depletion or ablation of endogenous Wnt2 inhibits CRC cell proliferation. Similarly, neutralizing secreted Wnt2 reduces Wnt target gene expression and suppresses CRC cell proliferation. Conversely, Wnt2 increases cell proliferation of intestinal epithelial cells. Intriguingly, WNT2 expression is transcriptionally silenced by EZH2-mediated H3K27me3 histone modification in non-CRC cells, However, WNT2 expression is de-repressed by the loss of PRC2's promoter occupancy in CRC cells. Our results reveal the unexpected roles of Wnt2 in complementing Wnt/β-catenin signaling for CRC cell proliferation.

| S-EPMC4741928 | biostudies-literature

Targeting the Wnt/β-catenin signaling pathway in cancer.

Project description:The aberrant Wnt/β-catenin signaling pathway facilitates cancer stem cell renewal, cell proliferation and differentiation, thus exerting crucial roles in tumorigenesis and therapy response. Accumulated investigations highlight the therapeutic potential of agents targeting Wnt/β-catenin signaling in cancer. Wnt ligand/ receptor interface, β-catenin destruction complex and TCF/β-catenin transcription complex are key components of the cascade and have been targeted with interventions in preclinical and clinical evaluations. This scoping review aims at outlining the latest progress on the current approaches and perspectives of Wnt/β-catenin signaling pathway targeted therapy in various cancer types. Better understanding of the updates on the inhibitors, antagonists and activators of Wnt/β-catenin pathway rationalizes innovative strategies for personalized cancer treatment. Further investigations are warranted to confirm precise and secure targeted agents and achieve optimal use with clinical benefits in malignant diseases.

| S-EPMC7716495 | biostudies-literature

Axitinib blocks Wnt/β-catenin signaling and directs asymmetric cell division in cancer.

Project description:Oncogenic mutations of the Wnt (wingless)/β-catenin pathway are frequently observed in major cancer types. Thus far, however, no therapeutic agent targeting Wnt/β-catenin signaling is available for clinical use. Here we demonstrate that axitinib, a clinically approved drug, strikingly blocks Wnt/β-catenin signaling in cancer cells, zebrafish, and Apc(min/+) mice. Notably, axitinib dramatically induces Wnt asymmetry and nonrandom DNA segregation in cancer cells by promoting nuclear β-catenin degradation independent of the GSK3β (glycogen synthase kinase3β)/APC (adenomatous polyposis coli) complex. Using a DARTS (drug affinity-responsive target stability) assay coupled to 2D-DIGE (2D difference in gel electrophoresis) and mass spectrometry, we have identified the E3 ubiquitin ligase SHPRH (SNF2, histone-linker, PHD and RING finger domain-containing helicase) as the direct target of axitinib in blocking Wnt/β-catenin signaling. Treatment with axitinib stabilizes SHPRH and thereby increases the ubiquitination and degradation of β-catenin. Our findings suggest a previously unreported mechanism of nuclear β-catenin regulation and indicate that axitinib, a clinically approved drug, would provide therapeutic benefits for cancer patients with aberrant nuclear β-catenin activation.

| S-EPMC4995957 | biostudies-literature

LncCCAT1 Promotes Breast Cancer Stem Cell Function through Activating WNT/β-catenin Signaling.

Project description:Background: Breast cancer stem cells (BCSCs) play an essential role in facilitating breast cancer relapse and metastasis. The underlying mechanism, however, remains incompletely understood. In the current study, we investigated the clinical significance, biological function and mechanism of a long noncoding RNA CCAT1 (LncCCAT1) in BCSCs. Methods: Firstly, lncRNAs expression in poorly differentiated breast cancer tissues and BCSCs were measured by lncRNA microarray and confirmed in breast cancer tissues and cell lines. The functional roles and mechanisms of LncCCAT1 were further investigated by gain and loss of function assays in vitro and in vivo. Results: LncCCAT1 is markedly upregulated in breast cancer tissues BCSCs and is correlated with poor outcomes in breast cancer patients. Overexpression of LncCCAT1 contributes to the proliferation, stemness, migration and invasion capacities of BCSCs. Mechanistic investigation suggests that LncCCAT1 can interact with miR-204/211, miR-148a/152 and Annexin A2(ANXA2), then upregulate T-cell factor 4 (TCF4) or promote translocation of β-catenin to the nucleus where it activates TCF4, leading to the activation of wingless/integrated (Wnt) signaling. Furthermore, TCF4 can also bind to the promoter of LncCCAT1 to promote LncCCAT1 transcription, thus forming a positive feedback regulatory circuit of LncCCAT1-TCF4-LncCCAT1 in BCSCs. Conclusions: LncCCAT1 plays an important role in breast cancer progression and may serve as a novel target for breast cancer diagnosis and therapy.

| S-EPMC6831302 | biostudies-literature

The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway.

Project description:The ability to harness innate immunity is a promising solution for improving cancer immunotherapy. Interferon (IFN) induces expression of IFN-stimulated genes (ISGs) by activating the JAK-STAT signaling pathway to promote innate immunity and inhibit malignant tumor growth, but the functions and mechanisms of most ISGs in cancer regulation are unknown. As an innate immune effector, ISG12a promotes the innate immune response to viral infection. In this study, ISG12a was found to be expressed at low levels in gastrointestinal cancer, represented by hepatocellular cancer (HCC) and gastric cancer (GC), and it identified as a tumor suppressor that affects clinical prognosis. ISG12a silencing accelerated the malignant transformation and epithelial-mesenchymal transition of cancer cells. Mechanistically, ISG12a promoted β-catenin proteasomal degradation by inhibiting the degradation of ubiquitinated Axin, thereby suppressing the canonical Wnt/β-catenin signaling pathway. Notably, β-catenin was identified as a transcription factor for PD-L1. Inhibition of Wnt/β-catenin signaling by ISG12a suppressed expression of the immune checkpoint PD-L1, rendering cancer cells sensitive to NK cell-mediated killing. This study reveals a mechanism underlying the anticancer effects of IFN. Some ISGs, as represented by ISG12a, may be useful in cancer therapy and prevention. The identified interrelations among innate immunity, Wnt/β-catenin signaling, and cancer immunity may provide new insight into strategies that will improve the efficiency of immunotherapy.

| S-EPMC7784998 | biostudies-literature

Wnt/β-Catenin Signaling and Immunotherapy Resistance: Lessons for the Treatment of Urothelial Carcinoma.

Project description:Urothelial cell carcinoma (UCC) is a significant public health burden. It accounts for approximately 90 percent of all bladder cancers with an estimated 200,000 annual deaths globally. Platinum based cytotoxic chemotherapy combinations are the current standard of care in the frontline setting for metastatic UCC. Even with these treatments the median overall survival is estimated to be about 15 months. Recently, immune checkpoint inhibitors (ICIs) have demonstrated superior clinical benefits compared to second line chemotherapy in UCC treatment. However only a minority of patients (~20%) respond to ICIs, which highlights the need to better understand the mechanisms behind resistance. In this review, we (i) examine the pathophysiology of Wnt/β-catenin signaling, (ii) discuss pre-clinical evidence that supports the combination of Wnt/β-catenin inhibitors and ICI, and (iii) propose future combination treatments that could be investigated through clinical trials.

| S-EPMC7924395 | biostudies-literature

Fibulin-5 inhibits Wnt/β-catenin signaling in lung cancer.

Project description:Metastatic lung cancer is incurable and a leading cause of cancer death in the United States. However, the molecular mechanism by which lung cancer cells invade other tissues has remained unclear. We previously identified fibulin-5, an extracellular matrix protein, as a frequently silenced gene in lung cancer and a suppressor of cell invasion. In this study, we found fibulin-5 functions by inhibiting the Wnt/β-catenin pathway. The Cancer Genome Atlas (TCGA) datasets show a strong association between loss of fibulin-5 expression and poor outcomes of lung cancer patients, and also activation of the Wnt target genes MMP-7 and c-Myc. Fibulin-5 impedes Wnt/β-catenin signaling by inhibiting extracellular signal-regulated kinase (ERK) to activate glycogen synthase kinase-3 β (GSK3β), which downregulates β-catenin and prevents its nuclear accumulation, leading to suppression of MMP-7 and c-Myc expression. These effects of fibulin-5 are mediated by its amino-terminal integrin-binding RGD motif. Fibulin-5 also blocks Wnt/β-catenin signaling in vivo in H460 metastasis and H1299 tumor models. Furthermore, knockdown of β-catenin suppresses metastasis of H460 tumors, while knockdown of GSK3β promotes metastasis of fibulin-5-expressing H1752 tumors. Together, our results suggest that fibulin-5 functions as a metastasis suppressor in lung cancer by modulating tumor microenvironment to suppress Wnt/β-catenin signaling.

| S-EPMC4558133 | biostudies-literature

DDAH1 mediates gastric cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway.

Project description:Gastric cancer (GC) represents the fourth most common malignant neoplasm and the second leading cause of cancer death. Despite therapeutic advances in recent decades, the clinical outcome remains dismal owing to the fact that most patients with GC show advanced disease at diagnosis and current chemotherapy only confers a modest survival advantage. Identification of key molecular signaling pathways involved in gastric carcinogenesis and progression would aid in early diagnosis and provide a rational design for targeted therapies in selected patients with advanced GC, to improve their outcome. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the main enzyme that can degrade asymmetric dimethylarginine, an endogenous nitric oxide synthase (NOS) inhibitor. Increased DDAH1 expression and NO production have been linked to multiple pathological conditions including cancer. However, the prognostic significance of DDAH1 in patients with GC and its function in GC progression remain undefined. In this study, we found that downregulation of DDAH1 was frequently detected in GC tissues and strongly correlated with more aggressive phenotypes and poor prognosis. Functional assays confirmed that forced expression of DDAH1 in the GC cells suppressed cell migration and invasion in vitro, as well as metastatic potential in vivo. DDAH1 overexpression inhibited the epithelial-mesenchymal transition process by increasing β-catenin degradation through the attenuation of Wnt/GSK-3β signaling. In contrast, knockdown of DDAH1 produced the opposite effect. These findings suggest that DDAH1 functions as a tumor suppressor in GC and may be exploited as a diagnostic and prognostic biomarker for GC.

| S-EPMC5579338 | biostudies-literature

ADMA mediates gastric cancer cell migration and invasion via Wnt/β-catenin signaling pathway.

Project description:ObjectiveTo explore the role of ADMA in gastric cancer.MethodsThe specimens of 115 gastric cancer patients were analyzed by ELISA and survival analysis. Functional assays were used to assess the effects of ADMA on gastric cancer cells. Experiments were conducted to detect the signaling pathway induced by ADMA in GC.ResultsGastric cancer patients with high ADMA levels had poor prognosis and low survival rate. Furthermore, high level of ADMA did not affect the proliferation while promoted the migration and invasion of gastric cancer cell. Moreover, ADMA enhanced the epithelial-mesenchymal transition (EMT). Importantly, ADMA positively regulated β-catenin expression in GC and promoted GC migration and invasion via Wnt/β-catenin pathway.ConclusionsADMA regulates gastric cancer cell migration and invasion via Wnt/β-catenin signaling pathway and which may be applied to clinical practice as a diagnostic and prognostic biomarker.

| S-EPMC7854427 | biostudies-literature

Palladin promotes cancer stem cell-like properties in lung cancer by activating Wnt/Β-Catenin signaling.

Project description:BackgroundCancer stem cells (CSCs) are responsible for drug resistance, cancer relapse, and metastasis. Here, we report the first analysis of Palladin expression and its impacts on stem cell-like properties in lung cancer.MethodsTissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo.ResultsBy using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell-like properties, including cell viability, invasion, migration, self-renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of β-catenin and activated Wnt/β-catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and β-catenin. Wnt/β-catenin pathway inhibitor blocked the Palladin-induced enhancement of sphere-forming.ConclusionsPalladin might act as an oncogene by promoting CSCs-like properties and tumorigenicity of NSCLC cells via the Wnt/β-catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs.

| S-EPMC9972019 | 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