文章：

Shkbp1基因敲除小鼠肿瘤生长和转移的抑制作用

Suppression of tumor growth and metastasis in Shkbp1 knockout mice 

原文发布日期：2021-06-10 

英文摘要：

Epidermal growth factor receptor (EGFR) is widely accepted in cancer diagnosis and targeted therapy. Shkbp1 is an upstream molecule of EGFR, which prevents EGFR degradation. However, the role of Shkbp1 in tumor remains to be clarified. Herein we induced tumor in the lungs of Shkbp1 knockout mice with chemical drugs to investigate the function of Shkbp1. Compared with wild-type mice, tumors in the lungs were significantly fewer in Shkbp1 knockout mice. To further explore the biological characteristics and functions of Shkbp1 in cancer cells, we established cell lines with overexpression and low expression of Shkbp1, respectively. Results from our experiments showed that low expression of Shkbp1 in lung cancer remarkably inhibited cancer cell migration and invasion, while overexpression of Shkbp1 promoted their migration and invasion, which indicated that Shkbp1 was closely related with tumor migration and invasion. The mRNA expression analysis of 494 matched tumor and adjacent non-tumor tissues (data derived from TCGA database) revealed that Shkbp1 was associated with the clinic TNM staging. Furthermore, immunohistochemistry (IHC) analysis of tissue microarrays showed that Shkbp1 was also correlated with lymphatic metastasis. Mechanistically, we observed that Shkbp1 was associated with epithelial–mesenchymal transition (EMT) marker. More interestingly, Shkbp1 was also expressed in a variety of immune cells, and we hereby used a subcutaneous transplantation tumor model and a metastasis model created by tail vein injection to explore whether Shkbp1 could impact tumor growth. The results showed that Shkbp1 knockout reduced tumor growth in both tumor models. In general, our results suggest that knocking out Shkbp1 in either immune cells or tumor cells could suppress tumor growth and metastasis. 

摘要翻译： 

表皮生长因子受体（EGFR）在癌症诊断与靶向治疗中已被广泛认可。Shkbp1作为EGFR的上游分子，能够阻止EGFR降解。然而，Shkbp1在肿瘤中的作用尚待阐明。本研究通过化学药物诱导Shkbp1基因敲除小鼠肺部肿瘤形成，以探究Shkbp1的功能。与野生型小鼠相比，Shkbp1敲除小鼠肺部肿瘤数量显著减少。为进一步探索Shkbp1在癌细胞中的生物学特性和功能，我们分别建立了Shkbp1过表达和低表达的细胞系。实验结果表明：Shkbp1低表达显著抑制肺癌细胞迁移和侵袭，而过表达则促进其迁移侵袭，提示Shkbp1与肿瘤迁移侵袭密切相关。通过对TCGA数据库中494对匹配的肿瘤与癌旁组织进行mRNA表达分析，发现Shkbp1与临床TNM分期相关。组织芯片的免疫组化（IHC）分析进一步显示，Shkbp1与淋巴转移存在关联。在机制层面，我们观察到Shkbp1与上皮-间质转化（EMT）标志物相关。更有趣的是，Shkbp1在多种免疫细胞中亦有表达，我们通过皮下移植瘤模型和尾静脉注射建立的转移模型，探究了Shkbp1是否影响肿瘤生长。结果显示：在两种肿瘤模型中，Shkbp1敲除均能抑制肿瘤生长。总体而言，我们的研究结果表明，无论在免疫细胞还是肿瘤细胞中敲除Shkbp1，均可抑制肿瘤生长和转移。

原文链接：

Suppression of tumor growth and metastasis in Shkbp1 knockout mice