Up‐regulation of TINAGL1 promotes gastric cancer growth and metastasis by regulating multiple MMPs expression

BACKGROUND AND AIM Tubulointerstitial nephritis antigen like 1 (TINAGL1), as a novel matricellular protein, has been demonstrated to participate in cancer progression, whereas the potential function of TINAGL1 in gastric cancer (GC) remains unknown. METHODS The expression pattern of TINAGL1 in GC was examined by immunohistochemistry, ELISA, real-time PCR and western blot. Correlation between TINAGL1 and MMPs analyzed by the GEPIA website and KM plots database. The lentivirus based TINAGL1 knockdown, CCK-8, Transwell assays were used to test the function of TINAGL1 in vitro. The role of TINAGL1 was confirmed by subcutaneous xenograft, abdominal dissemination, and lung metastasis model. Microarray experiments, ELISA, real-time PCR and western blot were used to identify molecular mechanism. RESULTS TINAGL1 was increased in GC tumor tissues and associated with poor patient survival. Moreover, TINAGL1 significantly promoted GC cell proliferation and migration in vitro as well as facilitated GC tumor growth and metastasis in vivo. TINAGL1 expression in GC cells was accompanied with increasing matrix metalloproteinases (MMPs) including MMP2, MMP9, MMP11, MMP14 and MMP16. GEPIA database revealed that these MMPs were correlated with TINAGL1 in GC tumors, and that the most highly-expressed MMP was MMP2. Mechanically, TINAGL1 regulated MMP2 through the JNK signaling pathway activation. CONCLUSIONS Our data highlight that TINAGL1 promotes GC growth and metastasis and regulates MMP2 expression, indicating that TINAGL1 may serve as a therapeutic target for GC.