scholarly journals Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation

2020 ◽  
Vol 21 (15) ◽  
pp. 5495
Author(s):  
Lai-Sheung Chan ◽  
Hong-Lok Lung ◽  
Roger Kai-Cheong Ngan ◽  
Anne Wing-Mui Lee ◽  
Sai Wah Tsao ◽  
...  
Keyword(s):  
Cell Migration ◽  
Nasopharyngeal Carcinoma ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Integration Site ◽  
Wnt Signaling Pathway ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Tumor Sphere ◽  
Sphere Formation

The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres. Subsequent studies indicated ICG-001 inhibited EVI1 expression via upregulated expression of miR-96. Results from EVI1 3′UTR luciferase reporter assay confirmed that EVI1 is a direct target of miR-96. Further mechanistic studies revealed that ICG-001, overexpression of miR-96, or knockdown of EVI1 expression could restore the expression of miR-449a. The suppressive effect of miR-449a on the cell migration and tumor sphere formation was confirmed in NPC cells. Taken together, the miR-96/EVI1/miR-449a axis is a novel pathway involved in ICG-001-mediated inhibition of NPC cell migration and growth of the tumor spheres.

scholarly journals RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3192
Author(s):  
Antoine Gleizes ◽  
Mouna Triki ◽  
Sandrine Bonnet ◽  
Naomi Baccari ◽  
Gabriel Jimenez-Dominguez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Differentiation ◽  
Paneth Cell ◽  
Wnt Signaling Pathway ◽  
Cell Lineage ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Sox9 Expression ◽  
Human Colon Cancer

RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.

scholarly journals Genetic Polymorphism in Extracellular Regulators of Wnt Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Garima Sharma ◽  
Ashish Ranjan Sharma ◽  
Eun-Min Seo ◽  
Ju-Suk Nam
Keyword(s):  
Genetic Polymorphism ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
The Other ◽  
Present Review ◽  
Receptor Complex ◽  
Related Proteins ◽  
Related Association

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.

ribbon encodes a novel BTB/POZ protein required for directed cell migration in Drosophila melanogaster

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 3001-3015 ◽  
Author(s):  
Pamela L. Bradley ◽  
Deborah J. Andrew
Keyword(s):  
Cell Migration ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Egf Receptor ◽  
Tracheal System ◽  
Directed Cell Migration ◽  
Posterior Migration ◽  
And Function ◽  
Dorsal Epidermis ◽  
Anterior Posterior

During development, directed cell migration is crucial for achieving proper shape and function of organs. One well-studied example is the embryonic development of the larval tracheal system of Drosophila, in which at least four signaling pathways coordinate cell migration to form an elaborate branched network essential for oxygen delivery throughout the larva. FGF signaling is required for guided migration of all tracheal branches, whereas the DPP, EGF receptor, and Wingless/WNT signaling pathways each mediate the formation of specific subsets of branches. Here, we characterize ribbon, which encodes a BTB/POZ-containing protein required for specific tracheal branch migration. In ribbon mutant tracheae, the dorsal trunk fails to form, and ventral branches are stunted; however, directed migrations of the dorsal and visceral branches are largely unaffected. The dorsal trunk also fails to form when FGF or Wingless/WNT signaling is lost, and we show that ribbon functions downstream of, or parallel to, these pathways to promote anterior-posterior migration. Directed cell migration of the salivary gland and dorsal epidermis are also affected in ribbon mutants, suggesting that conserved mechanisms may be employed to orient cell migrations in multiple tissues during development.

scholarly journals LncRNA HCG11 promotes proliferation and migration in gastric cancer via targeting miR-1276/CTNNB1 and activating Wnt signaling pathway

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hua Zhang ◽  
Haitao Huang ◽  
Xiaomei Xu ◽  
Haiying Wang ◽  
Jianxiang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Function Analysis ◽  
Wnt Signaling Pathway ◽  
Tumor Formation ◽  
Tumor Promoter ◽  
Luciferase Reporter ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Gastric cancer (GC) is one common cancer which occurs in the stomach leading to high mortality around the world. Long non-coding RNAs (lncRNAs) were found overexpressed or silenced in the occurrence and progression of multiple cancers including GC. Method The gene expression level in GC tissues and cells were analyzed by RT-qPCR. CCK-8, colony formation, flow cytometry and transwell assays were performed for the function analysis of HLA complex group 11 (HCG11). The mechanism study for HCG11 was conducted using RIP, RNA pull down and luciferase reporter assays. Results HCG11 was discovered highly expressed in GC tissues and cells. Depletion experiments were used to evaluate HCG11 silence on cell proliferation, migration and apoptosis. Moreover, Wnt signaling pathway was found as a tumor promoter in GC. RIP assay, RNA pull down assay and luciferase reporter assay were performed to illustrate the relationship of HCG11, miR-1276 and CTNNB1. Rescue assays revealed that HCG11/miR-1276/CTNNB1 axis regulated the incidence and development of GC. Tumor formation in mice proved that HCG11 was negatively correlated with miR-1276 and had positively correlation with CTNNB1. Conclusion Overall, HCG11 accelerated proliferation and migration in GC through miR-1276/CTNNB1 and Wnt signaling pathway, revealing that HCG11 could be a brand new target for GC.

scholarly journals Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin

2019 ◽  
Vol 20 (21) ◽  
pp. 5391 ◽  
Author(s):  
Wörthmüller ◽  
Salicio ◽  
Oberson ◽  
Blum ◽  
Schwaller
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Expression System ◽  
Single Agent ◽  
Wnt Signaling Pathway ◽  
Tumor Formation ◽  
Mesenchymal Transition

Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca2+-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells’ growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.

scholarly journals The role of WNT signaling in adult ovarian folliculogenesis

Reproduction ◽  
2015 ◽  
Vol 150 (4) ◽  
pp. R137-R148 ◽  
Author(s):  
J A Hernandez Gifford
Keyword(s):  
Wnt Signaling ◽  
Hormonal Regulation ◽  
Ovarian Function ◽  
Integration Site ◽  
Ovarian Follicle ◽  
Wnt Signaling Pathway ◽  
Signaling Molecules ◽  
Steroid Production ◽  
Downstream Signaling ◽  
Follicle Maturation

Wingless-type mouse mammary tumor virus integration site (WNT) signaling molecules are locally secreted glycoproteins that play important role in regulation of ovarian follicle maturation and steroid production. Components of the WNT signaling pathway have been demonstrated to impact reproductive functions, including embryonic development of the sex organs and regulation of follicle maturation controlling steroidogenesis in the postnatal ovary. Emerging evidence underscores the complexity of WNT signaling molecules in regulation of dynamic changes that occur in the ovary during the reproductive cycle. While disruption in the WNT signaling cascade has been recognized to have deleterious consequences to normal sexual development, more recent studies are beginning to highlight the importance of these molecules in adult ovarian function related to follicle development, corpus luteum formation, steroid production and fertility. Hormonal regulation of WNT genes and expression of members of the WNT signaling network, including WNT ligands, frizzled receptors, and downstream signaling components that are expressed in the postnatal ovary at distinct stages of the estrous cycle suggest a crucial role in normal ovarian function. Similarly, FSH stimulation of T-cell factor-dependent gene expression requires input from β-catenin, a lynchpin molecule in canonical WNT signaling, further indicating β-catenin participation in regulation of follicle maturation. This review will focus on the multiple functions of WNT signaling in folliculogenesis in the adult ovary.

scholarly journals CXCL12 mediates T‐cell migration via activation of the non‐canonical Wnt signaling pathway

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Manik C. Ghosh ◽  
Gary D Collins ◽  
Arnell Carter ◽  
Bolormaa Vandanmagsar ◽  
Margaret Brill ◽  
...  
Keyword(s):  
Cell Migration ◽  
T Cell ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Canonical Wnt Signaling ◽  
T Cell Migration ◽  
Canonical Wnt

scholarly journals Misregulation of Wnt Signaling Pathways at the Plasma Membrane in Brain and Metabolic Diseases

Membranes ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 844
Author(s):  
Mustafa Karabicici ◽  
Yagmur Azbazdar ◽  
Evin Iscan ◽  
Gunes Ozhan
Keyword(s):  
Plasma Membrane ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Metabolic Diseases ◽  
Wnt Signaling Pathway ◽  
Membrane Domains ◽  
Physiological Processes ◽  
Pathway Activation ◽  
Wnt Pathways ◽  
Membrane Components

Wnt signaling pathways constitute a group of signal transduction pathways that direct many physiological processes, such as development, growth, and differentiation. Dysregulation of these pathways is thus associated with many pathological processes, including neurodegenerative diseases, metabolic disorders, and cancer. At the same time, alterations are observed in plasma membrane compositions, lipid organizations, and ordered membrane domains in brain and metabolic diseases that are associated with Wnt signaling pathway activation. Here, we discuss the relationships between plasma membrane components—specifically ligands, (co) receptors, and extracellular or membrane-associated modulators—to activate Wnt pathways in several brain and metabolic diseases. Thus, the Wnt–receptor complex can be targeted based on the composition and organization of the plasma membrane, in order to develop effective targeted therapy drugs.

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