Rac1 mediates behaviors of leukemic cells in response to down-regulation of E-cadherin expression

AIM: To investigate the effect of E-cadherin down-regulation on the behaviors of leukemic cells and its molecular mechanism, and to further determine the role of abnormal interactions between hematopoietic progenitor and bone marrow microenvironment in leukogenesis. METHODS: E-cadherin was silenced via small RNA interference in Raji leukemic cells and 293T stroma cells. The ability of cell-cell adhesion was determined by cell adhesion assay after E-cadherin was knockdown. Adhesion associated proliferation was examined by MTT assay after plating Raji cells onto 293T cells. The expression of Rho GTPase Rac1 was determined by Western blotting. RESULTS: After E-cadherin was silenced in Raji and 293T cells, the ability of cell-cell homophilic adhesion was reduced significantly and the proliferation of Raji cells cultured on 293T cells was promoted significantly. Additionally, siRNA mediated silencing of E-cadherin in Raji cells resulted in up-regulation of Rac1 protein. CONCLUSION: Silencing the expression of E-cadherin in leukemic cells results in decreased adhesion and enhanced proliferation of leukemic cells. Inhibition of E-cadherin expression is responsible for the malignant behaviors of leukemia cells, which may be mediated by Rac1 GTPase.