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Notum Leads to Potential Pro-survival of OSCC Through Crosstalk Between Shh and Wnt/β-catenin Signaling Via p-GSK3β

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机构: [1]Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China. [2]Department of Orthodontics, Sichuan University, West China Hospital of Stomatology, State Key laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Chengdu 610041, China. [3]Life Science Institute of Jinzhou Medical University, College of Basic Medicine of Jinzhou Medical University, Cell Biology and Genetic Department of Jinzhou Medical University, Key Lab of Molecular and Cellular Biology of the Education Department of Liaoning Province, Jinzhou 121001, China. [4]Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
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关键词: OSCC Notum Proliferation Migration P-GSK3β

摘要:
Notum, which belongs to the α/β hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms. Various approaches including bioinformatics analysis, enzyme-linked immunosorbent assay and immunohistochemical staining were used to detect the expression of Notum in OSCC cells and tissues. Cell counting kit-8 assay, clone formation assay, wound healing assay, transwell assay and in-gel zymography assay were explored to evaluate the regulation of Notum in OSCC proliferation and migration. Hoechst 33342/PI assay, cell immunofluorescence, flow cytometry and in vivo tumorigenesis experiment were applied for OSCC apoptosis. Real-time quantitative polymerase chain reaction analysis was performed for mRNA level while western blotting was conducted to detect protein expression. The results showed that Notum was highly expressed in OSCC tissues and cells, and Notum promoted the proliferation and migration of OSCC cells while it inhibited their apoptosis. Furthermore, signaling pathway analysis showed that Notum led to potential pro-survival of OSCC through crosstalk between sonic hedgehog (Shh) and Wnt/β-catenin signaling via phosphorylation of glycogen synthase kinase-3 beta. These results will help to elucidate the mechanism and also provide new ideas for targeted treatment of OSCC.Copyright © 2022 Elsevier Ltd. All rights reserved.

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 3 区 生化与分子生物学 3 区 细胞生物学
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学 3 区 细胞生物学
第一作者:
第一作者机构: [1]Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China.
通讯作者:
通讯机构: [1]Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China. [*1]Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong KeyLaboratory of Oral Tissue Regeneration & Shandong Engineering Laboratoryfor Dental Materials and Oral Tissue Regeneration, Wenhua West Road 44-1, Jinan 250012, China.
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