While not generally associated with the lung and CF, is a growing concern as a human pathogen. Adherence and colonization of Serratia in the trachea would putatively also be modulated by normal mucocilliary clearance mechanisms. Alterations in ENaC regulation may disrupt these normal processes and represent one potential mechanism by which serralysin facilitates Serratia infection in the trachea. Consistent with this, recent work evaluating the effects of Liddle syndrome mutants in ENaC demonstrates that tracheal tissue is sensitive to alterations in ENaC activity. Dysregulation of ENaC results in increased Na + flux and an increase in fluid absorption in isolated murine trachea overexpressing b-ENaC under thin film conditions. Similarly, studies of fluid secretion using isolated pig and human trachea and specific channel blockers for CFTR and ENaC demonstrate that both channels contribute to secretion and ASL fluid maintenance. Thus, either inhibition or hyper-activation of these channels would potentially alter fluid balance in the airway. Finally, the inhibition seen with the AP Inh suggests a general mechanism by which this group of protease virulence factors may be partially neutralized. The small, soluble protease inhibitor appears stable and effective for prolonged periods in vitro and under a variety of physiological conditions. These characteristics are likely the result of strong SB431542 selective pressure to protect the pathogen from unregulated intracellular protease activities. Given the strong structural similarity between other members of this family of metalloproteases, it is likely that this inhibitor could inhibit other structurally similar proteases and may be useful in efforts to modulate other serrlaysin or related proteases. Communication between the epithelial and stromal compartments is fundamental in the modulation of normal epithelial homeostasis which becomes dysregulated during carcinogenesis due to genetic and epigenetic alterations. Regarding these compartments myofibroblasts represent ultimate members of the information flow. Myofibroblasts become primarily mesenchymal elements during the development of colorectal cancer and may play a crucial role in the process of field cancerization. The theory of field cancerization describes the formation of a genetically and epigenetically altered, but histologically normal field around the primary tumor. These genetic and epigenetic changes could contribute to the altered epithelial homeostasis, characterized by increased cell proliferation and predispose to the development of cancer in morphologically normal adjacent tumor areas. In some cases, between tumoral and NAT areas, a transitional area was identified, which displayed a different degree of dysplasia. Although several studies have already described NSC 136476 molecular abnormalities in association with field cancerization in epithelial tumors including CRC, the exact role of stroma in this process is still unclear. Here, we aim to examine the potential role of stroma-derived Wnt inhibitor secreted frizzled-related protein 1 in CRC field cancerization. SFRP1 inhibits proliferation and induces apoptosis by directly binding to Wnt-1 and Wnt-5 ligands via preventing the activation of Wnt receptors and low-density lipoprotein receptor-related protein-5 and 6 ). This system is dysregulated in around 90% of sporadic CRC patients due to aberrant canonical Wnt signaling, including mutation of cytoplasmic b-catenin degradation complex proteins, such as Adenomatous Polyposis Coli and Axin. In 5% of CRC cases, b-catenin is mutated and does not undergo proteasomal degradation via failed phosphorylation by GSK3b. Mutation of the Wnt pathway results in inappropriate nuclear b-catenin migration, accumulation and T-cell factor /lymphocyte enhanced factor activation.