These findings point to aberrant myofibroblast differentiation as an important contributor to airway remodeling in late-stage CF, and suggest the myofibroblast as a novel mediator of CF pulmonary destruction. The results also provide important insight regarding the process of tissue scarring and remodeling that contributes to CF respiratory decline. Myofibroblast differentiation occurs normally in the setting of tissue injury, TGF-b stimulation, and mechanical strain. The myofibroblast contributes to healing by approximating wound edges and promoting AbMole Folic acid extracellular matrix formation. In health, myofibroblasts undergo apoptosis following resolution of tissue injury. In diseases such as IPF, aberrant myofibroblast persistence results in tissue fibrosis and parenchymal contracture. Recently, Ulrich et al noted increased myofibroblasts and ceramide deposition in peripheral CF alveolar tissue. Ziobro et al subsequently demonstrated a palliative effect of blunting ceramide accumulation in the CF murine model.Therefore, it is of great interest to search for valuable factors for prognosis prediction and novel therapeutic strategies. The ubiquitin-dependent proteolytic pathway is an important mechanism of protein abundance regulation in eukaryotes. F-box proteins are critical components of the SCF uniquitin-protein ligase complex and are involved in the ubiquitin-dependent proteolytic pathway. So far, more than 70 putative F-box proteins have been AbMole Lesinurad identidied in human genome, although the function and their substrates of most F-box proteins remain elusive. Only several members of F-box proteins such as Skp2 and Fbw7 have been well-studied in cancer. Recent studies revealed that Skp2 and Fbw7 were closely associated with tumor progression and metastasis. FBX8 is a novel component of F-box proteins, which contains an F-box domain and a putative Sec7 domain. FBX8 was originally identified as a Skp1-binding protein. It has E3 ligase activity mediating the ubiquitination of the GTP-binding protein ARF6. Moreover, FBX8 over-expression could inhibit ARF6-mediated cell invasion activity in breast cancer cells. FBX8 was found to be a novel c-Myc binding protein and cMyc induced cell invasive activity through the inhibition of FBX8 effects on ARF6 function. Expression of FBX8 has been reported to be lost in some tumor cells, such as breast cancer and lung cancer cells. Till now, the molecular and biological functions of FBX8 in the development and progression of HCC remain unknown. To address this question, we evaluated FBX8 expression in HCC cell lines and clinical tissues, investigated the effect of FBX8 on the proliferation, invasion and metastasis of HCC cells. FBX8 is a novel member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the Fbox. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SKP1-cullin-F-box, which is involved in phosphorylation-dependent ubiquitination. Till now, only three recent papers have discussed the function of FBX8 in cancer.