WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer [patients]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA679738 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR13091226.fastq.gz | Fastqsanger.gz | |||
| SRR13091227.fastq.gz | Fastqsanger.gz | |||
| SRR13091228.fastq.gz | Fastqsanger.gz | |||
| SRR13091229.fastq.gz | Fastqsanger.gz | |||
| SRR13091230.fastq.gz | Fastqsanger.gz |
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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
Project description: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.
2022-02-21 | GSE161865 | GEO
Project description:WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer
| PRJNA679736 | ENA
Project description:BackgroundBreast cancer has been associated with activation of the WNT signaling pathway, although no driver mutations in WNT genes have been found yet. Instead, a high expression of the alternative WNT receptor ROR2 was observed, in particular in breast cancer brain metastases. However, its respective ligand and downstream signaling in this context remained unknown.MethodsWe modulated the expression of ROR2 in human breast cancer cells and characterized their gene and protein expression by RNA-Seq, qRT-PCR, immunoblots and reverse phase protein array (RPPA) combined with network analyses to understand the molecular basis of ROR2 signaling in breast cancer. Using co-immunoprecipitations, we verified the interaction of ROR2 with the identified ligand, WNT11. The functional consequences of WNT11/ROR2 signaling for tumor cell aggressiveness were assessed by microscopy, impedance sensing as well as viability and invasion assays. To evaluate the translational significance of our findings, we performed gene set enrichment, expression and survival analyses on human breast cancer brain metastases.ResultsWe found ROR2 to be highly expressed in aggressive breast tumors and associated with worse metastasis-free survival. ROR2 overexpression induced a BRCAness-like phenotype in a cell-context specific manner and rendered cells resistant to PARP inhibition. High levels of ROR2 were furthermore associated with defects in cell morphology and cell-cell-contacts leading to increased tumor invasiveness. On a molecular level, ROR2 overexpression upregulated several non-canonical WNT ligands, in particular WNT11. Co-immunoprecipitation confirmed that WNT11 indeed interacts with the cysteine-rich domain of ROR2 and triggers its invasion-promoting signaling via RHO/ROCK. Knockdown of WNT11 reversed the pro-invasive phenotype and the cellular changes in ROR2-overexpressing cells.ConclusionsTaken together, our study revealed a novel auto-stimulatory loop in which ROR2 triggers the expression of its own ligand, WNT11, resulting in enhanced tumor invasion associated with breast cancer metastasis.
| S-EPMC8672621 | biostudies-literature
Project description:WNT11 is a novel ligand for ROR2 in human breast cancer
| PRJNA679735 | ENA
Project description:ROR2 is a type I orphan-receptor tyrosine-kinase-like membrane protein. Its expression level is decreased after birth and barely detectable in adulthood. However, it is re-expressed by various cancer cells and is negatively correlated with patients' survival. The role of ROR2 in breast cancer is still unknown.This study demonstrated that ROR2 activates RhoA GTPase, and induces EMT in breast cancer. In addition, ROR2 is enriched in breast CSCs and required for maintaining the stemness features of CSCs. We developed a ROR2 specific antibody that inhibits breast cancer primary tumor growth and metastasis through targeting CSCs.
2024-12-17 | GSE191159 | GEO
Project description:Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a plasma membrane proteoglycan, is highly expressed in intestinal subtype gastric tumours and that this signature associates with patients’ poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer motility and invasion. We also find that SDC4 conjugated with heparan sulfate chains is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis of the molecular implications of SDC4 expression in gastric cancer cells and open new perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumour progression.
2023-05-05 | PXD035679 | Pride
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
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
Project description:Microarray analyses revealed distinct gene expression alterations in the luminal and basal epithelial compartments in the absence of Ror2 with marked alterations observed in genes associated with actin filament-based processes and the actin cytoskeletal network. Given that Ror2 expression resides in both basal and luminal epithelial cells, we wanted to identify compartment-specific functions for Ror2 in coordinating development. Accordingly, luminal and basal epithelial cell populations from shLUC and shRor2 outgrowths were isolated by FACS separation on the basis of CD24 and CD29 surface marker expression and gene expression analysis was subsequently performed using Agilent microarrays.
2015-01-09 | E-GEOD-57985 | biostudies-arrayexpress