Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion
Figure 2
Dynamic adherens junctions. Prostaglandins influence the assembly, stabilization, and disassembly of cell-cell junctions. E-cadherins form Ca2+-dependent transmembrane adhesion complexes between adjacent cells (Figure 2). Cytoplasmic regulatory proteins include α-catenin, β-catenin, IQGAPs scaffold proteins that interact with Rho GTPases to alter morphology and migration. Alternate interactions involve δ-catenin, p190, and RhoA influencing actin assembly. Together, Src and p140Cap influence C-terminal Src kinase (Csk) activity stabilizing cell-cell interactions as well as similar activity by receptor protein tyrosine phosphatase mu (PTPμ). Nectins-afadin complexes also cooperate with cadherins and integrins to regulate cell-cell adhesion. Disassembly of cadherin complexes involves either caveolin- or clathrin-mediated endocytosis and phagosome formation. Inside-out vesicles contain cadherin on the inside and β-catenin and Src exposed to the cytoplasm. When these vesicles interact with Ras-related protein A (RalA), cadherins are recycled. Whereas, interactions with Ras-proximate-1/Ras-related protein-1-(Rap1-)GTPase and E3 ubiquitin ligase followed by ubiquitinization result in proteosomal degradation that prepares cells for migration. The loss of E-cadherin in conjunction with elevations in COX-2 occurs during the transformation and adenoma formation in the presence of Apc mutations causing aberrant β-catenin signaling. Subsequent interactions with T-cell factor/lymphoid-enhancer-factor-(TCF/LEF-) can cause increases in COX-2 expression.
