The Role of Wnt and R-spondin in the Stomach During Health and Disease

The Wnt signaling pathway is one of the most prominent developmental signals. In addition to its functions in development, there is emerging evidence that it is also crucial for various organ functions in adult organisms, where Wnt signaling controls tissue stem cell behavior, proliferation and differentiation. Deregulation of Wnt signaling is involved in various pathological conditions and has been linked to malignant tissue transformation in different organ systems. The study of the Wnt signaling pathway has revealed a complex regulatory network that tightly balances the quality and strength of Wnt signaling in tissues. In this context, R-spondins are secreted proteins that stabilize Wnt receptors and enhance Wnt signaling. In this review we focus on new insights into the regulatory function of Wnt and R-spondin signaling in the stomach. In addition to its function in the healthy state, we highlight the connection between Wnt signaling and infection with Helicobacter pylori (H. pylori), a pathogen that colonizes the stomach and is the main risk factor for gastric cancer. In addition to experimental data that link Wnt signaling to carcinogenesis, we discuss that Wnt signaling is affected in a substantial proportion of patients with gastric cancer, and provide examples for potential clinical implications for altered Wnt signaling in gastric cancer.

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Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer

Life ◽

10.3390/life11060522 ◽

2021 ◽

Vol 11 (6) ◽

pp. 522

Author(s):

Dehua Liu ◽

Chenyu Sun ◽

Nahyun Kim ◽

Chandur Bhan ◽

John Pocholo Whitaker Tuason ◽

...

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Prognostic Value ◽

Immune Cell ◽

System Development ◽

Wnt Signaling Pathway ◽

Immune System Development ◽

Precision Therapy ◽

Gastric Cancer Patients

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

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GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway

Cancer Cell International ◽

10.1186/s12935-020-01692-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Hong Chen ◽

Lu Xu ◽

Zhi-li Shan ◽

Shu Chen ◽

Hao Hu

Keyword(s):

Gastric Cancer ◽

Transcription Factor ◽

Western Blot ◽

Wnt Signaling ◽

Cancer Cells ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Cancer Tissues

Abstract Background Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.

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

Cancer Cell International ◽

10.1186/s12935-019-1046-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

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.

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