文章：

结缔组织生长因子在调控上皮表型中的新作用

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype

原文发布日期：2 October 2023

DOI: 10.3390/cancers15194834

类型: Article

开放获取: 是

英文摘要：

Background: Epithelial–mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between the epithelial and mesenchymal stage is essential for tissue homeostasis. Many of the genes promoting mesenchymal transformation have been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify the genes responsible for maintaining the epithelial phenotype and inhibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expression was determined via qPCR and Western blot analysis. The knockout of CTGF was completed using the CTGF sgRNA CRISPR/CAS9. The tumorigenic potential was determined using NCG mice. Results: The knockout of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as anoikis resistance, cytoskeleton remodeling, increased cell stiffness, and the acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with the early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for the conservation of epithelial structure and function. These findings provide a new window into understanding the early stages of mesenchymal transformation.

摘要翻译： 

背景：上皮-间质转化（EMT）是一种生物学过程，其中上皮细胞失去其黏附特性并获得侵袭性、转移性和间质特性。维持上皮与间质阶段之间的平衡对组织稳态至关重要。虽然已发现许多促进间质转化的基因，但我们对维持上皮表型相关基因的理解仍有限。本研究旨在鉴定负责维持上皮表型并抑制EMT的基因。方法：利用体外EMT模型进行RNA测序分析，通过qPCR和Western blot检测CTGF表达水平，采用CTGF sgRNA CRISPR/CAS9技术敲除CTGF基因，并利用NCG小鼠模型评估致瘤潜能。结果：在上皮性卵巢癌细胞中敲除CTGF基因后，细胞获得与间质表型相关的功能特征，包括失巢凋亡抵抗、细胞骨架重塑、细胞硬度增加以及侵袭和致瘤能力增强。结论：本研究发现CTGF是维持上皮表型的重要调控因子，其缺失与EMT所需的早期细胞改变相关。我们揭示了CTGF在调控细胞骨架及细胞外基质相互作用中的新功能，这些相互作用对维持上皮结构和功能至关重要。该发现为理解间质转化的早期阶段提供了新的视角。

原文链接：

A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype