Tartrate-resistant acid phosphatase 5/ACP5 interacts with P53 to control the expression of SMAD3 in lung adenocarcinoma

Abstract Tartrate-resistant acid phosphatase 5 (TRAP/ACP5) involves the development and prognosis of multiple tumors in previous studies, however, the mechanism in lung cancer is still unclear, 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 patients 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 mouse model. Additionally, mechanistic studies revealed 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 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.