Ror2-mediated non-canonical Wnt signaling regulates Cdc42 and cell proliferation during root development
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE161395 | GEO | 2020/11/13
REPOSITORIES: GEO
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Project description:Ror2-mediated non-canonical Wnt signaling regulates Cdc42 and cell proliferation during root development
| PRJNA678015 | ENA
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
Project description:During embryonic organogenesis, the odontogenic potential resides in dental mesenchyme from the bud stage until birth. Mouse dental mesenchymal cells (mDMCs) isolated from the inductive dental mesenchyme of developing molars are frequently used in the context of tooth development and regeneration. cultured mDMCs could retain the odontogenic potential for 24 h with a ratio of 60% for tooth formation, but mDMCs were incapable of supporting tooth formation after more than 24 h in culture. To reveal the underlying mechanism of the impairment of odontogenic potential, we generated gene expression profiles from mDMCs in culture using RNA-seq.
2016-10-31 | GSE78228 | GEO
Project description:We previously showed that the combination of markers LNGFR+ and THY-1+ can be used selectively to isolate human mesenchymal stem cells (hMSCs) in bone marrow and several tissues. However, the molecular mechanisms regulating stemness of hMSCs remain to be elucidated. In this study, we found that Frizzled 5 (FZD5) and Receptor tyrosine kinase-like orphan receptor 2 (ROR2) were highly enriched in LNGFR+THY-1+ derived clones that retain a high potential for proliferation (rapidly expanding clones; RECs). WNT5A, the ligand of FZD5, causes FZD5 and ROR2 to co-localize and activates non-canonical Wnt pathway in RECs. Moreover, FZD5 knockdown attenuated proliferation and caused senescence. In contrast, FZD5 overexpression delayed senescence. These results indicate that intrinsic activation of non-canonical Wnt signaling via FZD5 and ROR2 modulates stemness and senescence of RECs. Thus, control of non-canonical Wnt signaling would enable us to regulate hMSC quality and to enhance the efficacy of cell-replacement therapy using hMSCs.
2016-09-02 | GSE86369 | GEO
Project description:BMP (bone morphogenetic protein) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that with binding of extracellular BMP ligands to the type I and type II transmembrane serine/threonine kinase receptor complexes when triggering of the BMP canonical signaling pathway, receptor activated Smad1/5/8 in cytoplasm bind to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, our recent studies reveal the functional operation of a novel BMP mediated signaling pathway named as the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In the current study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSmad1/5/8 is required for expression of MSX1, a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is indeed not operating in the early human developing tooth, as assessed by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and expression of MSX1 and translocation of pSMAD1/5/8 induced by BMP4 protein is SMAD4-independent in dental mesenchymal cells. Moreover, RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a manner of SMAD1/5/8-dependent but SMAD4-independent in the dental mesenchyme during early odontogenesis.
2021-09-30 | GSE179474 | GEO
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
Project description:RNA-Seq profiling of estrogen-receptor-positive MCF-7 cell lines with different perturbations of non-canonical WNT signaling . The MCF-7 cells were either transfected with an empty vector (pcDNA) or with a ROR2 overexpression construct, in parallel with or without stimulation with recombinant WNT5A. The objective was to find expression-responsive targets of these perturbations as potential drivers of increased cell invasiveness.
2017-08-17 | GSE74383 | GEO
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: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