文章：

结直肠癌进展与转移过程中巢蛋白-1/NID1的功能与调控机制研究

Nidogen-1/NID1 Function and Regulation during Progression and Metastasis of Colorectal Cancer

原文发布日期：7 November 2023

DOI: 10.3390/cancers15225316

类型: Article

开放获取: 是

英文摘要：

We have previously shown that the extracellular matrix and basement membrane protein Nidogen1 (NID1) is secreted by more malignant, mesenchymal-like CRC cells and induces the epithelial–mesenchymal transition (EMT) and promotes the migration and invasion of less malignant, epithelial-like CRC cells. Here, we performed a comprehensive bioinformatics analysis of multiple datasets derived from CRC patients and showed that elevated expression ofNID1and the genesITGA3,ITGB1, andITGAV,which encode NID1 receptors, is associated with poor prognosis and advanced tumor stage. Accordingly, the expression ofNID1,ITGA3,ITGB1, andITGAVwas associated with an EMT signature, which included SNAIL/SNAI1, an EMT-inducing transcription factor. In CRC cells, ectopic SNAIL expression induced NID1 and SNAIL occupancy was detected at an E-box upstream of theNID1transcription start site. Therefore,NID1represents a direct target of SNAIL. Ectopic expression of NID1 or treatment with NID1-containing medium endowed non-metastatic CRC cells with the capacity to form lung metastases after xenotransplantation into mice. Suppression of the NID1 receptor ITGAV decreased cell viability, particularly in CMS/consensus molecular subtype 4 CRC cells. Taken together, our results show thatNID1is a direct target of EMT-TF SNAIL and is associated with and promotes CRC progression and metastasis. Furthermore, the NID1 receptor ITGAV represents a candidate therapeutic target in CMS4 colorectal tumors.

摘要翻译： 

我们先前的研究表明，细胞外基质与基底膜蛋白Nidogen1（NID1）由恶性程度更高的间充质样结直肠癌细胞分泌，能够诱导上皮-间质转化（EMT），并促进恶性程度较低的上皮样结直肠癌细胞的迁移与侵袭。本研究通过对结直肠癌患者的多组数据集进行全面的生物信息学分析，发现NID1及其受体编码基因ITGA3、ITGB1和ITGAV的高表达与不良预后及晚期肿瘤分期相关。相应地，NID1、ITGA3、ITGB1和ITGAV的表达与EMT特征（包括EMT诱导转录因子SNAIL/SNAI1）存在关联。在结直肠癌细胞中，外源性SNAIL表达可诱导NID1表达，并在NID1转录起始位点上游的E-box区域检测到SNAIL结合。因此，NID1是SNAIL的直接靶基因。通过外源性表达NID1或使用含NID1培养基处理非转移性结直肠癌细胞后，这些细胞在异种移植至小鼠体内后获得肺转移能力。抑制NID1受体ITGAV可降低细胞活力，尤其在CMS/共识分子亚型4型结直肠癌细胞中效果显著。综上所述，我们的研究结果表明NID1是EMT转录因子SNAIL的直接靶标，参与并促进结直肠癌的进展与转移。此外，NID1受体ITGAV可作为CMS4型结直肠肿瘤的潜在治疗靶点。

原文链接：

Nidogen-1/NID1 Function and Regulation during Progression and Metastasis of Colorectal Cancer