Objective

Whether TEAD4 itself plays a vital role in the tumorigenesis and development of lung adenocarcinoma remains unclear. In our study, we aim to investigate the expression pattern and biological functions of TEAD4 and further investigate the potential mechanisms.

Methods

Clinical tumor and paired normal samples were collected for preparing tissue microarray. Western blot and immunohistochemical (IHC) staining of TEAD4 expression in these tissues were conducted to explore the expression pattern. Moreover, A549 cell line was select for investigating the function of TEAD4 for lung adenocarcinoma in vitro and in vivo. RNA sequencing was finally performed to further detect the potential downstream genes.

Results

The elevated TEAD4 expression level was observed in tumor tissues and the patients with higher TEAD4 expression tended to have worse overall survival. The knockdown of TEAD4 inhibits A549 cells proliferation ability and migration ability. A total of 431 differentially expressed genes (DEGs), including 239 down-regulated genes and 191 up-regulated genes, were finally identified and some of DEGs were validated. Moreover, knockdown of TEAD4 led to the down-regulation of pERK, which maybe the potential TEAD4-targeted signaling pathway to play the pro-tumorigenic function.

Conclusions

The expression level of TEAD4 is high in lung adenocarcinoma tumor tissues and positively associated with worse prognosis. Up-regulation of TEAD4 may lead to excessive transcription and phosphorylation of ERK proteins and therefore accelerates the process of tumor development. Our results demonstrate that overexpression of TEAD4 is a new mechanism of dysregulation of Hippo pathway.

中文翻译：

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TEAD4通过ERK信号通路促进肺腺癌患者的肿瘤发展。

目的

TEAD4本身是否在肺腺癌的发生和发展中起着至关重要的作用尚不清楚。在我们的研究中，我们旨在研究TEAD4的表达模式和生物学功能，并进一步研究其潜在机制。

方法

收集临床肿瘤和配对的正常样品以制备组织微阵列。在这些组织中进行了TEAD4表达的蛋白质印迹和免疫组化（IHC）染色，以探讨表达模式。此外，选择A549细胞系以研究TEAD4在体外和体内对肺腺癌的功能。最后进行RNA测序以进一步检测潜在的下游基因。

结果

在肿瘤组织中观察到升高的TEAD4表达水平，并且具有更高TEAD4表达的患者倾向于具有较差的总生存期。敲低TEAD4抑制A549细胞的增殖能力和迁移能力。最终鉴定出总共431个差异表达基因（DEG），包括239个下调基因和191个上调基因，并对其中一些DEG进行了验证。此外，敲低TEAD4导致pERK的下调，这可能是靶向TEAD4的潜在信号通路，发挥促肿瘤发生功能。

结论

TEAD4在肺腺癌肿瘤组织中的表达水平较高，与预后较差呈正相关。TEAD4的上调可能导致ERK蛋白的过度转录和磷酸化，因此加速了肿瘤的发展过程。我们的结果表明，TEAD4的过表达是河马途径失调的新机制。