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

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

PROVIDER: PRJNA679738 | ENA |

REPOSITORIES: ENA

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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 [patients]

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

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.

Project description: Not available

| S-EPMC8672621 | biostudies-literature

Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival

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

Gene transcript alterations exhibited in luminal and basal epithelial compartments with impaired Ror2 signaling

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

Knock down effect of Ror2 on gene expression profiling in human osteosarcoma cells (SaOS2)

Project description:Ror2 is a member of the Ror-family of receptor tyrosine kinases acting as a receptor for Wnt5a. Wnt5a/Ror2 signaling activates primarily the ß-catenin-independent pathway, which involves various signal mediators, such as Dishevelled, c-Jun N-terminal kinase (JNK), filamin A, c-Src, and Ca2+. Wnt5a/Ror2 signaling has also been shown to inhibit the ß-catenin-dependent pathway. Wnt5a and Ror2 are overexpressed in various types of tumor cells, including osteosarcoma and melanoma cells, resulting in constitutive activation of Wnt5a/Ror2 signaling in a cell-autonomous manner. Constitutively activated Wnt5a/Ror2 signaling has been shown to play important roles in promoting invadopodia formation and invasiveness of tumor cells. However, little is known about the mechanisms underlying these processes. As an attempt to understand the mechanism by which Wnt5a/Ror2 signaling, activated constitutively in osteosarcoma cells, contributes to their highly invasive properties, we performed DNA microarray analysis using a human osteosarcoma cell line, SaOS2.

2017-01-01 | GSE76535 | GEO

Expression and role of the receptor tyrosine kinase-like orphan receptor2 (ROR2) in small cell lung cancer

Project description:Heterogeneity of ROR2 was observed in the tumor tissues form patient-derived xenograft (PDX) model of SCLC, in which the cells with high ROR2 expression (ROR2high cell) and those without ROR2 expression (ROR2low cell) were gained and subjected to RNA sequence analysis. Cell proliferation activity was suppressed in ROR2 KO SBC3 cells in vitro and in vivo. Comparison of the downregulated DEG in the ROR2 KO SBC3 cells and the upregulated DEG in ROR2high cells in the PDX model revealed 135 common genes. After Metascape analysis of these genes, we focus on Aurora kinases. These results suggest that ROR2 could regulate cell cycle through AURKA and/or AURKB. This study clarrifies the function of ROR2 in SCLC with heterogeneous expression condition.

2022-12-15 | GSE210388 | GEO

Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients

Project description:Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.

2020-05-26 | E-MTAB-9112 | biostudies-arrayexpress

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