Tartrate-resistant Acid Phosphatase 5 Interacts With P53 To Regulate The Expression Of SMAD3 In Lung Adenocarcinoma

Objective: This study investigated the role of Tartrate-resistant acid phosphatase 5(ACP5)in the progression of lung adenocarcinoma.Methods: The relationship between ACP5 expression and lung adenocarcinoma patient prognosis was assessed.Mouse model,cytobiology and molecular biology assays were performed to elucidate the function and underlying mechanisms of ACP5 in lung adenocarcinoma.Results: 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,and invasion 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.Mechanistic studies revealed that ACP5 might regulate P53 phosphorylation at ser392,thereby enhancing the ubiquitination of P53,which then underwent degradation.Reducing the expression of P53 intensified the transcription of SMAD3,which promotes epithelial-mesenchymal transition in lung adenocarcinoma cells.Conclusions: ACP5 plays a key role in lung adenocarcinoma progression by inducing epithelial-mesenchymal transition via the regulation of P53/SMAD3 signaling.