Purpose: Metastatic prostate cancer (PCa) has become a major obstacle in the treatment of PCa. The study's purpose is to find biomarkers of tumor metastasis by proteomics and enzyme-linked immunosorbent assay (ELISA), and to design related experiments to study its role in the progress and metastasis of PCa. Method: We analyzed serum from primary PCa stage and metastatic stage of 12 patients to find metastatic PCa serum protein biomarkers using isobaric tags for relative and absolute quantitation (iTRAQ). An effective diagnostic model based on validated biomarkers using logistic regression was established. In vivo and in vitro biological behavior experiments (wound healing, CCK8, and Transwell tests) were carried out after obtaining the biomarkers. Related mechanism has been studied, which may be associated with metastatic PCa. Result: Actin gamma 1 (ACTG1) is a potential biomarker in the metastasis of PCa. Bioinformatics and related experiments show that ACTG1 is high-expressed in PCa tissues and cells. In vivo and in vitro experiments illustrated that the ability of proliferation, migration, and invasion of PCa cells was significantly inhibited after the knockdown of ACTG1 expression. Surprisingly, ERK protein expression was downregulated after ACTG1 knockdown. At the same time, the expression of epithelial-mesenchymal transition-related markers in PCa cells decrease after treated with ERK1/2 inhibitor, which indicating that ACTG1 may affect the metastatic ability of PCa cells through MAPK/ERK signaling pathway. Conclusion: ACTG1 is a marker of metastasis PCa. It mediates cell proliferation and may regulate the metastasis of PCa through MAPK/ERK signaling pathway, which provides a useful theoretical basis for exploring the treatment of PCa.
Keywords: ACTG1; ELISA; EMT; MAPK; iTRAQ; metastasis; prostate cancer.