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Objective:To explore the association of membrane-associated guanylate kinase inverted 1 (MAGI 1) with gastric cancer (GC) and the related molecular mechanisms.Methods:The reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC)were utilized to measure the MAGI1 expression level in GC tissues.Quantitative real-time PCR and West blotting were used to ensure the MAGI1 expression in GC cell lines.Small hairpin RNA (shRNA) was applied for knockdown of endogenous MAGI1 in GC cells.MTT assay and colony formation assay,scratch wounding migration assay and transwell chamber migration assay,as well as transwell chamber invasion assay were employed respectively to investigate the GC cell proliferation,migration and invasion in MAGI1-knockdown and control GC cells.The potential molecular mechanism mediated by MAGI1 was studied using West blotting and RT-PCR.Results:RT-PCR and IHC verified MAGI1 was frequendy expressed in matched adjacent noncancerous mucosa compared with GC tissues and the expression of MAGI 1 was related to clinical pathological parameters.Functional assays indicated that MAGI1 knockdown significantly promoted GC cell migration and invasion.Further mechanism investigation demonstrated that one pathway of MAGI 1 inhibiting migration and invasion was mainly by altering the expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT)-related molecules via inhibiting MAPK/ERK signaling pathway.Conclusions:MAGI1 was associated with GC clinical pathological parameters and acted as a tumor suppressor via inhibiting of MAPK/ERK signaling pathway in GC.