| ObjectiveMetadherin(MTDH)protein can be recruited to the mature tight junction complex,upregulate expression in many tumors and promote cancer metastasis.The aim of our study is to investigate the influence of MTDH expression on gastric cancer and to explore the potential mechnism of metastasis mediated by actin cytoskeletal remodeling via epithelial-mesenchyma transition(EMT).Materials and methodsRelative mRNA expression was assessed by q-PCR,and protein expression and location was tested by using immunohistochemistry staining,and the relationship between MTDH expression with clinical pathological features as well as the prognosis of patients with gastric cancer were analyzed.Transwell assay and wound healing assay were applied for the ability of invasion and metastasis in gastric cancer cells;skeleton protein(F-actin)staining assay was applied for the role of MTDH in regulating the morphology of gastric cancer cells,and the mechanism of MTDH in EMT process was studied by modulation of MTDH expression(RNA interference,RNAi)in gatric cancer cell lines.These functions of MTDH were further confirmed in vivo.ResultsWe found that MTDH was high expression in gastric cancer and MTDH expression was correlated with lymph node metastasis,TNM stage and decreased OS(P =0.002,<0.001 and 0.010,respectively).MTDH could promote EMT course invitro.Downregulation of MTDH expression inhibited migration and invasion in vitro and further suppressed tumour growth and metastasis in vivo.Downregulation of MTDH could regulate actin cytoskeleton remodeling and inhibit EMT,supporting that MTDH was a key role in cancer cell metastasis.ConclusionsMTDH can regulate actin cytoskeletal remodeling and enhance gastric cancer cell metastasis via epithelial-mesenchymal transition.What' s more,MTDH is an important factor for predicting metastasis and prognosis.It provides a new potential target for effective metastatic treatment. |
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