A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype.
A Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype.
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DOI：
10.3390/cancers15194834
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发表时间：
2023-10-02
期刊：
影响因子：
5.2
通讯作者：
Mor G
中科院分区：
文献类型：
--
作者：
Gogoi RP;Galoforo S;Fox A;Morris C;Ramos H;Gogoi VK;Chehade H;Adzibolosu NK;Shi C;Zhang J;Tedja R;Morris R;Alvero AB;Mor G
癌症的进展和转移与上皮细胞向间充质细胞的转化有关，这一过程称为上皮-间充质转化（epithelial - mesenchymal transition， EMT）。我们对促进EMT的基因有了更好的了解；不幸的是，我们对维持上皮表型的基因的理解是有限的。我们的目的是更好地了解阻止上皮细胞进行EMT的机制。我们发现CTGF是控制上皮表型的重要基因。它的丧失与EMT所需的早期细胞修饰有关。背景：上皮-间充质转化（epithelial - mesenchymal transition， EMT）是上皮细胞失去黏附特性而获得侵袭性、转移性和间充质特性的生物学过程。维持上皮和间充质阶段之间的平衡对组织稳态至关重要。许多促进间充质转化的基因已经被确定；然而，我们对维持上皮表型的基因的理解是有限的。我们的目的是确定负责维持上皮表型和抑制EMT的基因。方法：采用体外EMT模型进行RNA测序。通过qPCR和Western blot检测CTGF的表达。使用CTGF sgRNA CRISPR/CAS9完成CTGF的敲除。用NCG小鼠测定其致瘤潜能。结果：在上皮性卵巢癌细胞中敲除CTGF可获得与间充质表型相关的功能特征，如抗肿瘤、细胞骨架重塑、细胞刚度增加、获得侵袭和致瘤能力等。结论：我们发现CTGF是上皮表型的重要调节因子，其缺失与EMT所需的早期细胞修饰有关。我们描述了CTGF的新作用，调节细胞骨架和细胞外基质相互作用，这是保护上皮结构和功能所必需的。这些发现为理解间质转化的早期阶段提供了一个新的窗口。
Cancer progression and metastasis is associated with the transformation of epithelial cells into mesenchymal cells, a process known as epithelial–mesenchymal transition (EMT). We have a better understanding of the genes promoting EMT; unfortunately, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to better understand the mechanisms preventing epithelial cells from undergoing EMT. We identified CTGF as an essential gene controlling the epithelial phenotype. Its loss is associated with the early cellular modifications required for EMT. 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.
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