Abstract：
In a previous study, our research group observed that estrogen promotes the metastasis of non-small cell lung cancer (NSCLC) through the estrogen receptor β (ERβ). Invadopodia are key structures involved in tumor metastasis. However, it is unclear whether ERβ is involved in the promotion of NSCLC metastasis through invadopodia. In our study, we used scanning electron microscopy to observe the formation of invadopodia following the overexpression of ERβ and treatment with E2. In vitro experiments using multiple NSCLC cell lines demonstrated that ERβ can increase the formation of invadopodia and cell invasion. Mechanistic studies revealed that ERβ can upregulate the expression of ICAM1 by directly binding to estrogen-responsive elements (EREs) located on the ICAM1 promoter, which in turn can enhance the phosphorylation of Src/cortactin. We also confirmed these findings in vivo using an orthotopic lung transplantation mouse model, which validated the results obtained from the in vitro experiments. Finally, we examined the expressions of ERβ and ICAM1 using immunohistochemistry in both NSCLC tissue and paired metastatic lymph nodes. The results confirmed that ERβ promotes the formation of invadopodia in NSCLC cells through the ICAM1/p-Src/p-Cortactin signaling pathway.
摘要：
在之前的研究中,我们的研究组观察到雌激素通过雌激素受体β（ERβ）促进非小细胞肺癌（NSCLC）的转移。Invadopodia是参与肿瘤转移的关键结构。然而,目前尚不清楚ERβ是否通过侵入足来促进NSCLC转移。在我们的研究中,我们使用扫描电子显微镜观察了ERβ过表达和E2处理后invadopodia的形成。使用多种NSCLC细胞系的体外实验表明，ERβ可以增加侵袭足的形成和细胞侵袭。机制研究表明，ERβ可以通过直接与位于ICAM1启动子上的雌激素反应元件（EREs）结合来上调ICAM1的表达，这反过来可以增强Src/cortactin的磷酸化。我们还使用原位肺移植小鼠模型在体内证实了这些发现，验证了体外实验的结果。最后,我们使用免疫组织化学方法检测了ERβ和ICAM1在NSCLC组织和配对转移性淋巴结中的表达。结果证实,ERβ通过ICAM-1/p-Src/p-Cortactin信号通路促进NSCLC细胞内窝形成。
