Tumor-Host Interactions at the Metastatic Site: MKK4, Signal Transduction and the Stress Response

Abstract

The Mitogen-Activated Protein Kinase Kinase 4 (MKK4, also referred to as JNKK1, SEK2, or MEK4) has been identified as a metastasis suppressor gene in prostate and ovarian cancer. Metastasis suppressor genes are defined by the ability of their encoded proteins to suppress the development of metastases in vivo without affecting primary tumor growth when transfected into metastatic cell lines. Studies exploring the mechanisms of metastatic colonization and metastasis suppressor genes suggest that the critical events determining metastatic efficiency occur at the secondary site. Furthermore, metastasis suppressor proteins may operate by modulating major signal transduction pathways that regulate important cellular processes such as proliferation, differentiation, dormancy, and apoptosis. These findings have at least two important implications. First, tumor-host interactions at the metastatic site play an important role in the regulation of metastatic growth. Second, developing a comprehensive understanding of the specific biochemical events regulating both metastatic progression and metastatic suppression may ultimately contribute to new diagnostic and therapeutic modalities for advanced cancers.