Dataset Information

Ezrin promotes breast cancer progression by modulating AKT signals.

ABSTRACT:

Background

Ezrin, which is known as a cytoskeleton linker protein, is closely linked with the metastatic progression of cancer and is frequently abnormally expressed in aggressive cancer types. However, the possible involvement of Ezrin in metastasis and angiogenesis in breast cancer remains unclear.

Methods

Immunohistochemical analysis of Ezrin was performed on both BC samples (n = 117) and normal epithelium samples (n = 47). In vivo and in vitro assays were performed to validate the effect of Ezrin on AKT pathway-mediated BC progression.

Results

In this study, Ezrin was found to be upregulated in BC tissues, which was linked with aggressive tumour characteristics and poor prognosis. Moreover, we showed that Ezrin promotes BC proliferation, migration, invasion, and angiogenesis in vitro and in vivo. Mechanistic analysis showed that Ezrin interacted with AKT, and promoted its kinase activity, thereby regulating the AKT pathway in BC.

Conclusions

In all, we propose a model for an Ezrin/AKT oncoprotein axis, which provides novel insight into how Ezrin contributes to BC progression.

SUBMITTER: Li N

PROVIDER: S-EPMC6461860 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Ezrin promotes breast cancer progression by modulating AKT signals.

Li Nan N Kong Jienan J Lin Zhenhua Z Yang Yang Y Jin Tiefeng T Xu Ming M Sun Jie J Chen Liyan L

British journal of cancer 20190226 7

<h4>Background</h4>Ezrin, which is known as a cytoskeleton linker protein, is closely linked with the metastatic progression of cancer and is frequently abnormally expressed in aggressive cancer types. However, the possible involvement of Ezrin in metastasis and angiogenesis in breast cancer remains unclear.<h4>Methods</h4>Immunohistochemical analysis of Ezrin was performed on both BC samples (n = 117) and normal epithelium samples (n = 47). In vivo and in vitro assays were performed to validate ...[more]

PMID: 30804430

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Project description:PurposeCurrent knowledge of TMEM17, a recently identified protein of the transmembrane (TMEM) family, is limited, especially with respect to its expression and biological functions in malignant tumors. This study analyzed TMEM17 expression in invasive breast cancer tissue and breast cell lines and its relevance to clinicopathological factors, and investigated the mechanisms underlying the biological effects of TMEM17 on breast cancer cells.Patients and methodsTMEM17 protein expression was determined in 20 freshly harvested specimens (tumor and paired normal tissues) by Western blotting. Immunohistochemical analysis was performed to determine the expression and subcellular localization of TMEM17 in samples from 167 patients (mean age, 49 years) diagnosed with invasive ductal carcinoma (38 with triple-negative breast cancer; 129 with non-triple-negative breast cancer) who underwent complete resection in the First Affiliated Hospital of China Medical University between 2011 and 2013. Furthermore, TMEM17 was knocked down by small interfering RNAs in breast cancer cell lines.ResultsTMEM17 was found to be significantly upregulated in breast cancer tissues compared to the corresponding normal breast tissues by Western blotting (p=0.015). Immunohistochemical analysis revealed that TMEM was significantly upregulated in invasive breast cancer cells compared to adjacent normal breast duct glandular epithelial cells (10.78% vs 76.05%, p<0.001), and its expression was closely related to the patient's T-stage (p=0.022), advanced TNM stages (p=0.007), and lymph node metastasis (p=0.012). After TMEM17 knockdown or overexpression in breast cancer cell lines, TMEM17 upregulated p-AKT, p-GSK3β, active β-catenin, and Snail, and downstream target proteins c-myc and cyclin D1, and downregulated E-cadherin, resulting in increased cancer cell proliferation, invasion, and migration. These effects were reversed by the AKT inhibitor LY294002.ConclusionOur results indicate that TMEM17 is upregulated in breast cancer tissues and can promote malignant progression of breast cancer cells by activating the AKT/GSK3β signaling pathway.

Project description:BackgroundGastric cancer (GC) ranks among the most prevalent malignant neoplasms globally and is associated with a significant mortality rate. Despite the availability of various therapeutic interventions for GC, the overall prognosis for this disease remains unfavorable. This can be attributed to several factors, including delayed diagnosis and the inherent heterogeneity of the tumors. With the continuous enrichment of treatment methods, GC has entered an era of comprehensive treatment oriented toward precision and standardization.MethodsThrough the application of bioinformatics and assessments of tissue microarrays, this study has selected the histone chaperone Anti-Silencing Function 1B (ASF1B) for detailed analysis, including clinical specimens. We then constructed ASF1B knockout and overexpression cell lines, and conducted biological function tests on this basis, validated at mouse and organoid levels. Additionally, human immunereconstitution was performed in NOD-PrkdcscidIl2rgem1/Smoc (NSG) mice, followed by flow cytometry analysis of mouse blood. Mechanically, protein-protein interaction analyses were conducted utilizing Immunoprecipitation-Mass Spectrometry (IP-MS) and Tandem mass tagging (TMT) methodologies to identify protein clusters.ResultsThe analysis demonstrated that ASF1B is significantly upregulated in GC tissues and correlates with unfavorable prognostic outcomes. Biological function tests provided that ASF1B contributes to tumor cell proliferation, colony formation, invasion and migration, and plays an important role in the progression of GC in vivo. These findings were validated at both the mouse and organoid levels. Additionally, we observed that ASF1B is involved in the tumor microenvironment, where ASF1B knockdown increases CD8+ T cell infiltration, indicating a negative correlation with immune activation. Mechanically, our investigation revealed that ASF1B emerged as a promoter of GC progression by downregulating H2A clustered histone 20 (H2AC20), thereby influencing the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and extracellular regulated protein kinases (ERK)1/2 signaling pathways.ConclusionASF1B, recognized as an oncogene, contributes to the initiation and progression of tumors, positioning it as a prospective target for therapeutic intervention in GC.

Dataset Information

Ezrin promotes breast cancer progression by modulating AKT signals.

Background

Methods

Results

Conclusions

Publications

Ezrin promotes breast cancer progression by modulating AKT signals.

Similar Datasets

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