Showing 3 results for Wnt Signaling
Samaneh Saberi, Abbas Piryaei, Esmat Mirabzadeh, Maryam Esmaeili, Toktam Karimi, Sara Momtaz, Afshin Abdirad, Niloofar Sodeifi, Mohammad Ali Mohagheghi, Hossein Baharvand, Marjan Mohammadi,
Volume 23, Issue 2 (3-2019)
Abstract
Background: Two of the Wnt signaling pathway target genes, tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have examined their simultaneous expression in gastric carcinogenesis. Methods: Tumor and paired adjacent tissues of intestinal-type gastric cancer (GC) patients (n = 30) were evaluated for LGR5 and TROY expression by immunohistochemistry. The combination of the percentage of positively stained cells and the intensity of staining was defined as the composite score and compared between groups. The obtained findings were re-evaluated in a mouse model. Results: TROY expression in the tumor tissue was significantly lower than that of the adjacent tissue (2.5 ± 0.9 vs. 3.3 ± 0.9, p = 0.004), which was coincident with higher LGR5 expression (3.6 ± 1.1 vs. 2.7 ± 0.9, p = 0.001). This observation was prominent at stages II/III of GC, leading to a statistically significant mean difference of expression between these two molecules (p = 0.005). In the H. pylori infected-mouse model, this inverse expression was observed in transition from early (8-16 w) to late (26-50 w) time points, post treatment (p = 0.002). Conclusion: Our data demonstrates an inverse trend between TROY down-regulation and LGR5 up-regulation in GC tumors, as well as in response to H. pylori infection in mice. These findings support a potential negative modulatory role for TROY on LGR5 expression.
S Mahmoud A Najafi,
Volume 24, Issue 5 (9-2020)
Abstract
Precise regulation of signal transduction pathways is crucial for normal animal development and for maintaining cellular and tissue homeostasis in adults. The Wnt/Frizzled-mediated signaling includes canonical and non-canonical signal transduction pathways. Upregulation or downregulation of the canonical Wnt signaling (or the Wnt/β-Catenin signal transduction) leads to a variety of human diseases, including cancers, neurodegenerative disorders, skin and bone diseases, and heart deficiencies. Therefore, Wnt/β-Catenin signal transduction is a potential clinical target for the treatment of not only human cancers but also some other human chronic diseases. Here, some recent results including those from my laboratory highlighting the role of Wnt/β-Catenin signal transduction in human cancers will be reviewed. After a brief overview on canonical Wnt signaling and introducing some critical β-Catenin/T-cell factor-target genes, the interaction of canonical Wnt signaling with some common human cancers will be discussed. In the end, the different segments of the aforesaid signaling pathway, which have been considered as targets for clinical purposes, will be scrutinized.
Sara Ansari, Dr Sedighe Kolivand, Sara Salmanian, Marie Saghaeian Jazi, S Mahmoud A Najafi,
Volume 27, Issue 4 (7-2023)
Abstract
Background: The canonical Wnt signal transduction or the Wnt/β-catenin pathway plays a crucial role in both carcinogenesis and development of animals. Activation of the Gαq class of Gα proteins positively regulates Wnt/β-catenin pathway, and expression of Gαq in human embryonic kidney 293 (HEK293T) cells or Xenopus oocytes leads to the inhibition of glycogen synthase kinase-3 beta and cellular accumulation of β-catenin. This study investigated whether Gαq-mediated cellular accumulation of β-catenin could affect the transcriptional activity of this protein.
Methods: HEK-293T and HT-29 cells were used for cell culture and transfection. Protein localization and quantification were assessed by using immunofluorescence microscopy, cell fractionation assay, and Western blotting analysis. Gene expression at the transcription level was examined by quantitative reverse transcriptase/real-time PCR method.
Results: Transcription of two cellular β-catenin target genes (c-MYC and CCND1) and the β-catenin/ T-cell factor reporter luciferase gene (TopFlash plasmid) significantly increased by Gαq activation. The Gαq-mediated increase in the expression level of the β-catenin-target genes was sensitive to the expression of a minigene encoding a specific Gαq blocking peptide. The results of cell fractionation and Western blotting experiments showed that activation of Gαq signaling increased the intracellular β-catenin protein level, but it blocked its membrane localization.
Conclusion: Our results reveal that the Gαq-dependent cellular accumulation of β-catenin can enhance β-catenin transcriptional activity.
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