文章：

内质网应激与未分化甲状腺癌细胞系中的“间质化漂移”相关

ER Stress Is Associated with a “Mesenchymal Drift” in an Anaplastic Thyroid Carcinoma Cell Line

原文发布日期：31 October 2025

DOI: 10.3390/cancers17213534

类型: Article

开放获取: 是

英文摘要：

Background/Objectives:The tumor microenvironment (TME) plays a crucial role in the progression of the malignant phenotype through several mechanisms, such as hypoxia and nutrient deprivation, among others. These insults activate several intracellular pathways, and among them are ER stress and the unfolded protein response (UPR). Our aim was to assess if a specific ER stress inducer causes an exacerbation of the malignant phenotype of anaplastic thyroid carcinoma (ATC) cells.Methods:We used an ATC cell line, FRO cells, that had not undergone a full Epithelial–Mesenchymal Transition (EMT) and an ER stress-adapted cell line derived from FRO cells, A400 cells. Western blot, immunofluorescence, scratch, and invasion assays were used to evaluate the response of the FRO and A400 cells to ER stress.Results:The FRO cells were subjected to high-level ER stress caused by 400 ng/mL of tunicamycin (Tn). This caused the death of a large fraction of cells, but eventually a population emerged that we called A400 cells. Following an over challenge with Tn, the adapted population showed suppression of the UPR, apoptosis, and stress kinase activation. Moreover, the adapted population showed an exacerbation of mesenchymal features with a more invasive phenotype. At the level of a single cell, the adapted cells, caught in the act of moving, showed high-level expressions of vimentin (VIM), fibronectin (FN), and N-cadherin.Conclusions:High-level ER stress acts as a selection factor favoring the emergence of a cell population showing “mesenchymal drift” with a more malignant phenotype.

摘要翻译： 

背景/目的：肿瘤微环境通过缺氧与营养剥夺等多种机制在恶性表型进展中发挥关键作用。这些刺激因素可激活多条细胞内信号通路，其中内质网应激与未折叠蛋白反应尤为重要。本研究旨在探讨特定内质网应激诱导剂是否会加剧未分化甲状腺癌细胞的恶性表型。 方法：采用未完全经历上皮-间质转化的未分化甲状腺癌细胞系FRO及其衍生的内质网应激适应细胞系A400。通过蛋白质印迹、免疫荧光、划痕实验及侵袭实验评估两种细胞对内质网应激的反应。 结果：FRO细胞经400 ng/mL衣霉素处理后出现高水平内质网应激，导致大量细胞死亡，但最终形成命名为A400的细胞亚群。该适应细胞群在衣霉素超剂量刺激下表现出未折叠蛋白反应抑制、细胞凋亡减弱及应激激酶活化降低。此外，适应细胞群间质特征显著增强，呈现更具侵袭性的表型。单细胞水平分析显示，处于运动状态的适应细胞高表达波形蛋白、纤连蛋白及N-钙黏蛋白。 结论：高水平内质网应激可作为选择压力，促进具有"间质化漂移"特征且恶性程度更高的细胞亚群形成。

原文链接：

ER Stress Is Associated with a “Mesenchymal Drift” in an Anaplastic Thyroid Carcinoma Cell Line