Tartrate-resistant acid phosphatase 5 (TRAP/ACP5) has been shown to involve the development and prognosis of multiple tumors in previous studies; however, the mechanism in lung cancer is still unclear, and thus this study investigated the role of ACP5 in the progression of lung adenocarcinoma. After a series of in vitro and in vivo experiments, we observed that ACP5 expression was increased in lung adenocarcinomas (40/69, 57.97%); importantly, an increased ACP5 level was associated with patient age (p = 0.044) and lymph node metastasis (p = 0.0385). ACP5 overexpression significantly enhanced A549 and NCI-H1975 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and reduced cell apoptosis. Knocking down the expression of ACP5 could rescue the above cell phenotypes. Furthermore, enhancing ACP5 expression promoted lung adenocarcinoma cell hyperplasia and intrapulmonary metastasis in a mouse model. Additionally, mechanistic studies revealed that ACP5 might regulate p53 phosphorylation at Ser392, thereby enhancing the ubiquitination of p53, which then underwent degradation. Reducing the levels of p53 intensified the transcription of SMAD3, which promotes EMT in lung adenocarcinoma cells. In summary, the present study provides a theoretical basis and important scientific evidence on the key role of ACP5 in lung adenocarcinoma progression by inducing EMT via the regulation of p53/SMAD3 signaling.

耐酒石酸酸性磷酸酶5（TRAP / ACP5）参与了先前研究中多种肿瘤的发生和预后。然而，肺癌的机制仍不清楚，因此本研究调查了ACP5在肺腺癌进展中的作用。经过一系列的体内和体外实验中，我们观察到肺腺癌中ACP5表达增加（40 / 69，57.97％）；重要的是，ACP5水平升高与患者年龄（p = 0.044）和淋巴结转移（p = 0.0385）有关。ACP5过表达显着增强了A549和NCI-H1975细胞的增殖，迁移，侵袭和上皮-间质转化（EMT），并减少了细胞凋亡。降低ACP5的表达可以挽救上述细胞表型。此外，在小鼠模型中，增强ACP5表达可促进肺腺癌细胞增生和肺内转移。此外，机理研究表明，ACP5可能调节Ser392处的p53磷酸化，从而增强p53的泛素化，然后进行降解。降低p53的水平增强了p53的转录。SMAD3，在肺腺癌细胞中促进EMT。综上所述，本研究通过通过调控p53 / SMAD3信号诱导EMT，为ACP5在肺腺癌进展中的关键作用提供了理论基础和重要的科学证据。