Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the digestive tract in humans. Several studies have indicated that PAK4 is associated with the risk of ESCC and may be a potential druggable kinase for ESCC treatment. However, the underlying mechanism remains largely unknown. The aim of our study is to identify the functional role of PAK4 in ESCC. To determine the expression of PAK4 in ESCC, Western blot analysis and immunohistochemistry were performed, and the results showed that PAK4 is significantly upregulated in ESCC tissues and cell lines compared with normal controls and normal esophageal epithelial cell line. To further investigate the role of PAK4 in ESCC, cell viability assays, anchorage‐independent cell growth assays, wound healing assays, cellular invasion assays, in vivo xenograft mouse models, and metastasis assays were conducted, and the results showed that PAK4 can significantly facilitate ESCC proliferation and metastasis in vitro and in vivo. To determine the potential target of PAK4 in ESCC progression, a pull‐down assay was performed, and the results showed that LASP1 may be a potential target of PAK4. An immunoprecipitation assay and confocal microscopy analysis confirmed that PAK4 can bind to and colocalize with LASP1 in vitro and in cells. Notably, rescue experiments further illustrated the mechanistic network of PAK4/LASP1. Our research reveals the oncogenic roles of PAK4 in ESCC and preliminarily elucidates the mechanistic network of PAK4/LASP1 in ESCC.

中文翻译：

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p21激活的激酶4通过靶向LASP1促进食管鳞状细胞癌的发展

食道鳞状细胞癌（ESCC）是人类最常见的消化道恶性肿瘤之一。几项研究表明，PAK4与ESCC的风险有关，并且可能是ESCC治疗的潜在药物激酶。但是，基本机制仍然未知。我们研究的目的是确定PAK4在ESCC中的功能作用。为了确定PAK4在ESCC中的表达，进行了蛋白质印迹分析和免疫组化，结果表明与正常对照和正常食管上皮细胞系相比，PAK4在ESCC组织和细胞系中显着上调。为了进一步研究PAK4在ESCC中的作用，细胞活力测定，不依赖锚定的细胞生长测定，伤口愈合测定，细胞侵袭测定，体内异种移植小鼠模型，并进行了转移测定，结果表明PAK4可以显着促进ESCC在体内外的增殖和转移。为了确定ESCC进展中PAK4的潜在靶标，进行了一项下拉分析，结果表明LASP1可能是PAK4的潜在靶标。免疫沉淀测定和共聚焦显微镜分析证实，PAK4可以在体外和细胞中与LASP1结合并共定位。值得注意的是，救援实验进一步说明了PAK4 / LASP1的机制网络。我们的研究揭示了PAK4在ESCC中的致癌作用，并初步阐明了PAK4 / LASP1在ESCC中的机制网络。为了确定ESCC进展中PAK4的潜在靶标，进行了一项下拉分析，结果表明LASP1可能是PAK4的潜在靶标。免疫沉淀测定和共聚焦显微镜分析证实，PAK4可以在体外和细胞中与LASP1结合并共定位。值得注意的是，救援实验进一步说明了PAK4 / LASP1的机制网络。我们的研究揭示了PAK4在ESCC中的致癌作用，并初步阐明了PAK4 / LASP1在ESCC中的机制网络。为了确定ESCC进展中PAK4的潜在靶标，进行了一项下拉分析，结果表明LASP1可能是PAK4的潜在靶标。免疫沉淀测定和共聚焦显微镜分析证实，PAK4可以在体外和细胞中与LASP1结合并共定位。值得注意的是，救援实验进一步说明了PAK4 / LASP1的机制网络。我们的研究揭示了PAK4在ESCC中的致癌作用，并初步阐明了PAK4 / LASP1在ESCC中的机制网络。救援实验进一步说明了PAK4 / LASP1的机制网络。我们的研究揭示了PAK4在ESCC中的致癌作用，并初步阐明了PAK4 / LASP1在ESCC中的机制网络。救援实验进一步说明了PAK4 / LASP1的机制网络。我们的研究揭示了PAK4在ESCC中的致癌作用，并初步阐明了PAK4 / LASP1在ESCC中的机制网络。