ABSTRACT
Metastasis, the main cause of mortality in cancer patients, is a complex process consisting of several sequential, interlinked, and highly-selective steps. Fibroblast growth factor-inducible 14 (Fn14) is one member of the tumor necrosis factor receptor family, which is influential in controlling cell division, life, and death. The role of Fn14 in tumor metastasis regulation is slowly being unraveled, including roles in the regulation of the epithelial-mesenchymal transition, angiogenesis, cytoskeleton modulation, extracellular matrix degradation and inflammation. This review will focus on recent studies that demonstrate the involvement of Fn14 in tumor progression and will briefly describe various pathways of Fn14-regulated metastasis. Finally, future prospects will be discussed for the potential role of Fn14 as a predictive marker and therapeutic agent for tumor metastasis suppression.
Subject(s)
Cell Transformation, Neoplastic/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Neoplasms/genetics , Neovascularization, Pathologic/genetics , Receptors, Tumor Necrosis Factor/genetics , Animals , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Cytoskeleton/genetics , Cytoskeleton/metabolism , Cytoskeleton/ultrastructure , Humans , NF-kappa B/genetics , NF-kappa B/metabolism , Neoplasm Metastasis , Neoplasms/metabolism , Neoplasms/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Signal Transduction , TWEAK Receptor , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
The Tap protein mediates the sequence-specific nuclear export of mRNAs bearing the retroviral constitutive transport element (CTE) and also plays a critical role in the sequence nonspecific export of cellular mRNAs. Previously, we have demonstrated that CTE function displays species specificity, that is, the CTE functions in human but not quail cells. Here, we demonstrate that quail Tap fails to support CTE function because it cannot bind the CTE. However, changing a single residue in quail Tap, glutamine 246, to arginine, the residue found in human Tap, rescues both CTE function and CTE binding. This residue, which is located on the exterior of a recently reported molecular structure of Tap, defines a surface on Tap that is critical for CTE binding. These data emphasize the potential importance of cross-species genetic complementation in the identification and characterization of cellular factors that are critical for different aspects of viral replication.
