Ectodysplasin A receptor (EDAR) promotes colorectal cancer cell proliferation via regulation of the Wnt/β-catenin signaling pathway

Wang, Bin; Liang, Yuanxin; Chai, Xingxing; Chen, Shasha; Ye, Ziyu; Li, Ronggang; Li, Xiaoping; Kong, Gang; Li, Yanyun; Zhang, Xueying; Che, Zhengping; You, Yong‐Ke; Ye, Shicai; Li, Lili; Lin, Bihua; Huang, Juan; Huang, Ming-Yuan; Zhang, Xin; Qiu, Xiangyun; Zeng, Jincheng

doi:10.1016/j.yexcr.2020.112170

Cited by 18 publications

(19 citation statements)

References 25 publications

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“…Recent studies have demonstrated that EDA and its receptors participate in multiple signaling pathways, including the Wnt/β-catenin (Wang et al, 2020), c-Jun N-terminal kinase (JNK) (Sinha et al, 2002), bone morphogenetic protein (BMP)/Smad (Han et al, 2018), and fibroblast growth factor (FGF) signaling pathways (Häärä et al, 2012;Huh et al, 2013). Wang et al (2020) reported that EDAR promoted tumor cell proliferation by inducing Wnt/β-catenin signaling. The expression levels of genes related to the Wnt/β-catenin signaling pathway were upregulated in EDA high samples.…”

Section: Multiple Signaling Pathways Activated By Ectodysplasin Amentioning

confidence: 99%

Section: Multiple Signaling Pathways Activated By Ectodysplasin Amentioning

confidence: 99%

“…In patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), the plasma EDA content is high and is associated with deteriorating steatosis and fibrosis ( Bayliss et al, 2021 ). In addition to the effects on HED and metabolic disorders, several studies have reported that EDA and its receptors are involved in cancer pathogenesis by regulating the apoptosis, proliferation, differentiation, and migration of cancer cells ( Soraas and Stebbing, 2018 ; Vial et al, 2019 ; Li et al, 2020 ; Wang et al, 2020 ); however, this possibility remains controversial. Here, we review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles associated with EDA and its receptors.…”

Section: Introductionmentioning

confidence: 99%

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Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

et al. 2021

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Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.

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Section: Multiple Signaling Pathways Activated By Ectodysplasin Amentioning

confidence: 99%

Section: Multiple Signaling Pathways Activated By Ectodysplasin Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

et al. 2021

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“…The expression of PTPRZ1 is closely related to the KRAS mutation in CTC, which plays a vital role and exists widely in its occurrence (29). EDAR, which is up-regulated in CRC and has been confirmed to be a component of the Wnt/β-catenin signaling pathway, can also stimulate the proliferation of CRC in vitro (30).…”

Section: Statusmentioning

confidence: 99%

A methylation-based prognostic model predicts survival in patients with colorectal cancer

Tan¹,

Gui²,

Wang³

et al. 2021

J Gastrointest Oncol

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Background: To construct a model that could effectively predict the prognosis of colorectal cancer (CRC) by searching for methylated-differentially expressed genes (MDEGs).Methods: We identified MDEGs through four databases from Gene Expression Omnibus (GEO) and annotated their functions via bioinformatics analysis. Subsequently, after adjusting for gender, age, and grading, multivariate Cox hazard analysis was utilized to select MDEGs interrelated with the prognosis of CRC, and LASSO analysis was utilized to fit the prediction model in the training set. Furthermore, another independent dataset was harnessed to verify the effectiveness of the model in predicting prognosis.Results: In total, 252 hypomethylated and up-regulated genes and 132 hypermethylated and downregulated genes were identified, 27 of which were correlated with the prognosis of CRC, and a 10-gene prognostic model was established after LASSO analysis. The overall survival rate could be effectively grouped into different risks by the median score of this model in the training set [risk ratio (HR) =2.27, confidence interval (95% CI), 1.69-3.13, P=8.15×10 −8 ], and the validity of its effect in predicting prognosis in CRC was verified in the validation dataset (HR =1.75, 95% CI, 1.15-2.70, P=9.32×10 -3 ).Conclusions: Our model could effectively predict the overall survival rate of patients with CRC and provides potential application guidelines for its clinically personalized treatment.

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“…Staining was assessed semi-quantitatively under a light microscope at ×400 magnification by two independent observers, blinded to the origin of the tissue. The staining was evaluated according to the scoring criteria described previously (27). SNTB1 expression levels in CRC tissue samples were evaluated by the following staining index (SI) values: SI ≤4 was defined as weak staining or a low expression of SNTB1, and SI ≥6 was defined as strong staining or a high expression of SNTB1.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Beta-1 syntrophin (SNTB1) regulates colorectal cancer progression and stemness via regulation of the Wnt/β-catenin signaling pathway

Liang¹,

Wang²,

Chen³

et al. 2021

Ann Transl Med

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Background: Beta-1 syntrophin (SNTB1) is an intracellular scaffold protein that provides a platform for the formation of signal transduction complexes, thereby modulating and coordinating various intracellular signaling events and crucial cellular processes. However, the physiological role of SNTB1 is poorly understood. This study aims to explore the role of SNTB1 in colorectal cancer (CRC) tumorigenesis and progression, with particular focus on SNTB1's expression pattern, clinical relevance, and possible molecular mechanism in CRC development.Methods: SNTB1 expression was analyzed in both clinical tissues and The Cancer Genome Atlas (TCGA) database. Real-time polymerase chain reaction (PCR), Western blot, and immunohistochemical assays were used to detect the relative mRNA and protein levels of SNTB1. Statistical analysis was performed to examine the correlation between SNTB1 expression and the clinicopathological characteristics of patients with CRC.Bioinformatics gene set enrichment analysis (GSEA), Western blot, luciferase assay, and agonist recovery assays were conducted to evaluate the relevance of SNTB1 and the β-catenin signaling pathway in CRC. A flow cytometry-based Hoechst 33342 efflux assay was applied to assess the proportion of the side population (SP) within total CRC cells.Results: Elevated levels of SNTB1 were identified in CRC tissues and cell lines. The elevation of SNTB1 was positively correlated with the degree of malignancy and poor prognosis in CRC. We further revealed that, by modulating the β-catenin signaling pathway, silencing SNTB1 expression suppressed tumor growth and cancer stemness in vitro, as well as tumorigenesis in vivo.Conclusions: These findings suggest that SNTB1 plays a crucial role in colorectal tumorigenesis and Original ArticleLiang et al. SNTB1 regulates CRC progression and stemness

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Ectodysplasin A receptor (EDAR) promotes colorectal cancer cell proliferation via regulation of the Wnt/β-catenin signaling pathway

Cited by 18 publications

References 25 publications

Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

A methylation-based prognostic model predicts survival in patients with colorectal cancer

Beta-1 syntrophin (SNTB1) regulates colorectal cancer progression and stemness via regulation of the Wnt/β-catenin signaling pathway

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