Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer [patients]

ABSTRACT: Breast cancer is the most common cancer in women with more than two million new cases diagnosed in 2018. Patients frequently develop metastases in the course of their disease which limit survival due to the lack of a curative treatment. One signaling pathway that is frequently involved in cancer initiation and progression is the WNT pathway. Breast cancer has been associated with activation of the WNT signaling pathway, although the underlying molecular mechanisms are still unclear. Here, we found the WNT receptor ROR2 to be highly expressed in aggressive breast tumors and associated with worse metastasis-free survival. In this study we addressed this question and demonstrated for the first time that WNT11 is a novel ligand for ROR2 in humans. WNT11 binds to the CRD of ROR2 and mediates WNT/PCP signaling via the RHO/ROCK pathway that confers an aggressive phenotype to breast cancer cells. ROR2 and WNT11 are both highly expressed in human brain metastases and linked with short patient survival.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161865 | GEO | 2022/02/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer

Project description:Breast cancer has been associated with activation of the WNT signaling pathway, although the underlying molecular mechanisms are still unclear. In order to understand the molecular basis of these observations, we overexpressed ROR2 in human breast cancer cell lines and characterized them by RNA-Sequencing. High levels of ROR2 were associated with defects in cell morphology and cell-cell-contacts leading to increased tumor invasiveness. Using gene expression analysis we demonstrated an upregulation of several non-canonical WNT ligands in ROR2-overexpressing breast cancer cells, in particular WNT11. Knockdown of WNT11 reversed the pro-invasive phenotype and the cellular changes in ROR2-overexpressing cells. Taken together, our studies revealed a novel auto-stimulatory loop in which ROR2 triggers the expression of its own ligands, e.g. WNT11, resulting in enhanced tumor invasion associated with breast cancer metastasis.

2022-02-21 | GSE161864 | GEO

WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer

Project description:WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer

| PRJNA679736 | ENA

WNT11 is a novel ligand for ROR2 in human breast cancer

Project description:WNT11 is a novel ligand for ROR2 in human breast cancer

| PRJNA679735 | ENA

WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer [patients]

Project description:WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer [patients]

| PRJNA679738 | ENA

Cell fate and adhesion dynamics rely on Ror2-mediated alternative Wnt signaling during tumor progression

Project description:Cellular heterogeneity in breast cancer encompasses many features, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53 null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt b-catenin dependent signaling activity and noncanonical b-catenin independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo. We further discovered an antagonistic role for Ror2 in regulating canonical Wnt/b-catenin activity in vivo, where lentiviral shRNA depletion of Ror2 expression augmented canonical Wnt/b-catenin signaling activity across multiple basal-like models. Depletion of Ror2 expression yielded distinct phenotypic outcomes and divergent alterations in gene expression programs among different tumors, despite all sharing basal-like features. Notably, we uncovered cell state plasticity and adhesion dynamics regulated by Ror2, where Ras Homology Family Member A (RhoA) and Rho-Associated Coiled-Coil Kinase 1 (ROCK1) activity downstream of Dishevelled-2 (Dvl2) were implicated. Collectively, these studies illustrate the integration and collaboration of Wnt pathways in basal-like breast cancer, where Ror2 provides a spatiotemporal function to regulate the balance of Wnt signaling and cellular heterogeneity during tumor progression.

2017-01-23 | GSE93815 | GEO

Genome wide screen reveals WNT11, a noncanonical WNT gene, as a target of ETS transcription factor ERG

Project description:ERG is a transcription factor that is involved in leukomogenesis and its mRNA overexpression has been associated with poor prognosis in a subset of patients with T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Herein, a genome-wide screen of ERG target genes was conducted by chromatin immunoprecipitation-on-chip (ChIP-chip) in Jurkat cells. 342 significant annotated regions were derived from ChIP-chip experiments. Seventeen candidate promoter regions resulted in at least two-fold enrichment by quantitative PCR. Notably, ERG potential targets included WNT signaling genes: WNT2, WNT9A, WNT11, CCND1, and FZD7. Functionally, expression of WNT11 was downregulated with siRNA ERG knockdown and substantially upregulated in a tet-on ERG-inducible assay in K562 cells. To investigate a role for ERG in WNT signaling, a WNT agonist was used to inhibit glycogen synthase kinase (GSK-3). This treatment resulted in an ERG-dependent proliferative growth advantage in the tet-on ERG-inducible system. Lastly, chromatin immunoprecipitation assays of primary leukemia blasts confirmed WNT11 promoter enrichment dependent on ERG mRNA expression. In conclusion, ERG transcriptional networks in leukemia are revealed. Specifically, WNT11 emerged as a target of ERG. We propose that overexpression of ERG in acute leukemia may lead to a proliferative advantage upon activation of WNT signals. ChIP-chip with ERG antibody C20 and combined C17/20 and nonspecificic IgG in Jurkat

2010-12-10 | E-GEOD-21495 | biostudies-arrayexpress

Hedyotis diffusa-Sculellaria barbata (HD-SB) suppresses the progression of colorectal cancer cells via the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis

Project description:Our previous study confirmed that the combination of Hedyotis diffusa (HD) and Scutellaria barbata (SB) significantly inhibited colorectal cancer cells proliferation and the WNT signaling pathway. However, the exact molecular modulation remains unclear. In this study, colorectal cancer cells (SW620) were treated with 1 mg/mL HD-SB for 24 h, and high-throughput sequencing of circRNAs was performed. The level of hsa_circ_0039933 in three colorectal cancer cell lines (HT-29, SW620, and HCT116) was verified by qPCR. After transfection of hsa_circ_0039933 overexpression plasmids or small interfering RNAs, CCK8, apoptosis, cell migration, and cell invasion were utilized to evaluate the function of hsa_circ_0039933 in the progression of colorectal cancer cells. We identified hsa_circ_0039933, which was downregulated in HD-SB-induced colorectal cancer cells and positively related to colorectal cancer progression. In SW620 cells with relatively high expression of hsa_circ_0039933, interfering with the expression of hsa_circ_0039933 inhibited the proliferation, invasion, and migration of SW620 cells. In HCT116 cells with relatively low expression of hsa_circ_0039933, overexpression of hsa_circ_0039933 promoted the proliferation and invasion and migration ability of HCT116. Mechanistically, hsa_circ_0039933 targeted hsa-miR-204-5p to increase the expression of wnt11, leading to the activation of the Wnt pathway, thereby promoting the proliferation of colorectal cancer cells. This work revealed the potential molecular mechanism of HD-SB for the treatment of colorectal cancer, which was to inhibit the Wnt signaling pathway through the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis, then suppressing proliferation, migration, and invasion in colorectal cancer cell.

2023-08-16 | GSE237129 | GEO

Genome wide screen reveals WNT11, a noncanonical WNT gene, as a target of ETS transcription factor ERG

2010-12-10 | GSE21495 | GEO

Differential gene expression between wild type and Wnt11 mutant embryonic kidneys

Project description:The goal of this study was to identify changes in gene expression within nephron progenitors and the whole embryonic kidney between Wnt11 mutants and wild type animals. Wnt11 mutant kidneys have disorganized nephron progenitor niches. Ultimately, nephron endowment is reduced by 50% in Wnt11 mutants. Gene expression changes are minimal between mutant and wild type samples, suggesting Wnt11 may act through non-canonical, non-transcritional mechanisms to regulate kidney development.

2018-10-31 | GSE118334 | GEO

Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape mechanisms

Project description:Breast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2rÎ³-/- mice) we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases. Comparison of basal gene expression in breast cancer 4T1.2 cell line stably transfected using the pMSCV retroviral expression vector system with IRF7 or the base vector. Three independent experiments were performed comparing the IRF7 expressing cells to the base vector cells

2012-07-17 | E-GEOD-37828 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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