WNT5A Correlates with Clinicopathological Characteristics in Gastric Cancer: a Meta-Analysis

Nam, Seungyoon; Chung, Jun‐Won; Yang, Jun-Young

doi:10.1159/000455934

Cited by 17 publications

(14 citation statements)

References 25 publications

(29 reference statements)

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“…Inhibition of WNT5A by its antagonist, Box5, cancelled the CAFs' enhancing effects on cancer cell growth and migration. The prognostic impact of WNT5A expression was observed in the database, in line with previous studies 16 47…”

Section: Discussionsupporting

confidence: 90%

Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3

Maeda

Takeshima²,

Iida³

et al. 2019

Gut

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ObjectiveCancer-associated fibroblasts (CAFs), a major component of cancer stroma, can confer aggressive properties to cancer cells by secreting multiple factors. Their phenotypes are stably maintained, but the mechanisms are not fully understood. We aimed to show the critical role of epigenetic changes in CAFs in maintaining their tumour-promoting capacity and to show the validity of the epigenomic approach in identifying therapeutic targets from CAFs to starve cancer cells.DesignTwelve pairs of primary gastric CAFs and their corresponding non-CAFs (NCAFs) were established from surgical specimens. Genome-wide DNA methylation and H3K27me3 analyses were conducted by BeadArray 450K and ChIP-on-Chip, respectively. Functions of potential a therapeutic target were analysed by inhibiting it, and prognostic impact was assessed in a database.ResultsCAFs had diverse and distinct DNA methylation and H3K27me3 patterns compared with NCAFs. Loss of H3K27me3, but not DNA methylation, in CAFs was enriched for genes involved in stem cell niche, cell growth, tissue development and stromal–epithelial interactions, such as WNT5A, GREM1, NOG and IGF2. Among these, we revealed that WNT5A, which had been considered to be derived from cancer cells, was highly expressed in cancer stromal fibroblasts, and was associated with poor prognosis. Inhibition of secreted WNT5A from CAFs suppressed cancer cell growth and migration.ConclusionsH3K27me3 plays a crucial role in defining tumour-promoting capacities of CAFs, and multiple stem cell niche factors were secreted from CAFs due to loss of H3K27me3. The validity of the epigenetic approach to uncover therapeutic targets for cancer-starving therapy was demonstrated.

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Section: Discussionsupporting

confidence: 90%

Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3

Maeda

Takeshima²,

Iida³

et al. 2019

Gut

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“…Gastric cancer has become the 3rd leading cause for cancer death in the world ( 1 ), and ranks 1st in all malignant tumors in China. Most of the gastric cancer patients have been diagnosed as the adenocarcinoma type.…”

Section: Introductionmentioning

confidence: 99%

“…Most of the gastric cancer patients have been diagnosed as the adenocarcinoma type. Currently, pathogenesis of gastric cancer remains unknown due to the heterogeneity in histological and pathological features of gastric cancer, and the diagnostic rate in an early stage is relatively low; nowadays, resection has been used as the preferred option for treatment of gastric adenocarcinoma without distant metastasis ( 1 , 2 ). According to the literature, it is reported that tumor diameter, regional lymphatic metastasis, vascular invasion, pTNM stage and surgical method are major factors affecting the prognosis of gastric cancer patients ( 3 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

Analysis of survival and prognosis of 298 gastric adenocarcinoma patients with no distant metastasis

et al. 2017

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This study investigated the survival and prognosis of 298 gastric adenocarcinoma patients with no distant metastasis. For analysis and comparison of the prognosis of patients, a retrospective analysis was performed in 298 patients with perfect clinical data and follow-up data who received the D2 resections for gastric cancer in Shandong Provincial Hospital Affiliated to Shandong University between January, 2005 and January, 2012, and were diagnosed as gastric adenocarcinoma with no distant metastasis in postoperative pathological examination. Among the gastric adenocarcinoma patients without distant metastasis, we found that differences of sex, age, differentiation and position of tumor had no statistical significance (P>0.05), while comparisons of the tumor diameter, regional lymphatic metastasis, vascular invasion and pathological TNM stages (pTNM; T for tumor, N for lymph node and M for metastasis) showed statistical significance (P<0.05). One-way analysis of variance (ANOVA) indicated the correlation between the prognosis of gastric adenocarcinoma patients and tumor diameter, regional lymphatic metastasis, vascular invasion and pTNM stages of patients (P<0.05). Multivariate analysis of Cox regression models was performed for discovering the factors associated with the prognosis of patients, and the results suggested that position of tumor (P=0.016), regional lymphatic metastasis (P=0.042), vascular invasion (P=0.021) and pTNM stage (P=0.009) were the independent risk factors affecting the prognosis of gastric adenocarcinoma patients. During 60-month follow-up, the median survival duration of gastric adenocarcinoma patients with no distant metastasis was 38 months, while the 5-year accumulate survival rate was 49.3%. The results indicated that in gastric adenocarcinoma patients without distant metastasis, tumor diameter, regional lymphatic metastasis, vascular invasion and pTNM stage are major indicators affecting the prognosis of patients.

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“…Therefore, it remains possible that GC might proceed following not only Wnt5a overexpression but also impaired or unbalanced Wnt ligand availability. Finally, high Wnt5a expression is correlated with poor prognosis (Kurayoshi et al, 2006), and there is a statistically significant correlation between Wnt5a expression and several clinical parameters, such as lymph node metastasis and tumor depth (Nam et al, 2017).…”

Section: Wnt5a Expression In Gastric Cancermentioning

confidence: 97%

Wnt5a Signaling in Gastric Cancer

Astudillo

2020

Front. Cell Dev. Biol.

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Gastric cancer remains an important health challenge, accounting for a significant number of cancer-related deaths worldwide. Therefore, a deeper understanding of the molecular mechanisms involved in gastric cancer establishment and progression is highly desirable. The Wnt pathway plays a fundamental role in development, homeostasis, and disease, and abnormal Wnt signaling is commonly observed in several cancer types. Wnt5a, a ligand that activates the non-canonical branch of the Wnt pathway, can play a role as a tumor suppressor or by promoting cancer cell invasion and migration, although the molecular mechanisms explaining these roles have not been fully elucidated. Wnt5a is increased in gastric cancer samples; however, most gastric cancer cell lines seem to exhibit little expression of this ligand, thus raising the question about the source of this ligand in vivo. This review summarizes available research about Wnt5a expression and signaling in gastric cancer. In gastric cancer, Wnt5a promotes invasion and migration by modulating integrin adhesion turnover. Disheveled, a scaffolding protein with crucial roles in Wnt signaling, mediates the adhesion-related effects of Wnt5a in gastric cancer cells, and several studies provide growing support for a model whereby Disheveled-interacting proteins mediates Wnt5a signaling to modulate cytoskeleton dynamics. However, Wnt5a might induce other effects in gastric cancer cells, such as cell survival and induction of gene expression. On the other hand, the available evidence suggests that Wnt5a might be expressed by cells residing in the tumor microenvironment, where feedback mechanisms sustaining Wnt5a secretion and signaling might be established. This review analyzes the possible functions of Wnt5a in this pathological context and discusses potential links to mechanosensing and YAP/TAZ signaling.

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WNT5A Correlates with Clinicopathological Characteristics in Gastric Cancer: a Meta-Analysis

Cited by 17 publications

References 25 publications

Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3

Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3

Analysis of survival and prognosis of 298 gastric adenocarcinoma patients with no distant metastasis

Wnt5a Signaling in Gastric Cancer

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