In Vitro Rnai Down Erm Expression On Sgc Metastatic Ability

The metastatic spread of tumor is a multistep process that requires basal membrane invasion by the cells, their intravasation in blood or lymph vessels and their extravasation to reach and grow in distant tissues. At each step, cells undergo morphological changes driven by the cortical actin cytoskeleton. ERM (ezrin, radixin, moesin) family proteins provide a regulated linkage between the plasma membrane and the actin cytoskeleton. They have been implicated in the determination of cell shape, membrane organization, cell adherent, cell polarization, migration, division and they participate in various signaling pathways. Moreover, ezrin is now recognized as a key regulator of tumor metastasis. Upregulated ezrin expression is observed in the early steps of metastatic progression, it has been confirmed that the abnormal expression of ezrin is involved in the genesis, metastasis and prognosis of many kind of tumors such as gynecological tumors, digestive canal tumors, melanoma, pediatric osteosarcoma, rhabdomyosarcoma and so on. Recent studies in mice suggest redundant functions of the three proteins, but the evidence of the role of radixin and moesin in tumor metastasis has not been established. We sought to investigate whether radixin and moesin have the same function in tumor metastasis as that of ezrin. In present study, we chose human gastric carcinoma SGC cell expressing all ERM proteins as a model to examine their unique role in this matter. Using the RNAi method, ezrin, radixin and moesin stable knockdown SGC cells were constructed, which ensured the metastasis assay operated in optimal condition.In vitro cell migration and invasion experiments showed that all ERM specific deficiency caused the reduction of metastatic ability. Western blotting analysis showed that the expression of E-cadherin significantly increased when any ERM protein was down-regulated. Our results indicated that all ERM proteins play similar roles in the SGC cell metastasis and the mechanism between ezrin and E-cadherin may be important in their roles in tumor progression. This is a new evidence for ERM functional redundancy.