Small GTPase RJL Protects Tumor Cells Against Tumor Necrosis Factor-α-induced Cell Death And Promotes Tumor Metastasis

RJL is an oncogene candidate identified by us independently, which is possibly involved in the regulation of cell proliferation, cell cycle progression and tumorigenesis. Here we investigated the potential roles and mechanisms of RJL in protecting human breast cancer cells against tumor necrosis factorα(TNF-α)-induced apoptosis and promoting tumor metastasis. We demonstrated that RJL is an anti-apoptotic protein and may play a role in tumor metastasis. Overexpression of RJL in human breast cancer cell line MCF-7 could enhance TNF-α-induced PKB/Akt (protein kinase B) activation, and knockdown of RJL expression by small interferencing RNA duplexes decreased TNF-α-induced Akt phosphorylation. Overexpression or knockdown of RJL had no significant impact on the expression level of Bcl-2 family molecules and the activation of NF-κB signaling components. In addition, overexpression RJL could enchance the transcriptional activity of NF-κB and up-regulate the expression level of ICAM-1 (Intercellular adhesion molecule-1) and COX-2 (Cylcooxygenase-2), which are tumor metastasis-associated molecules. However, overexpression or knockdown of RJL did not influence expression level of tenascin-C which is also a NF-κB-regulated gene product involved in tumor cell attachment. These findings suggest that RJL may activate Akt via unknown mechanisms to protect tumor cells against TNF-αinduced cell death and that RJL may be involved in tumor metastasis through up-regulating tumor metastasis associated molecules.