P120～(ctn) Mediated Cell Adhesion And The Role Of Mangiferin In This Pathway

Catenin is an intracellular armadillo glycoprotein family, they are divided into 4 subfamilies: -, -, - (plakoglobin) and pl20ctncatenin. Catenin binds to the cytoplasmic tail of a transmembrane cell adhesion molecule-epithelial cadherin (E-cadherin) in epithelial cells and forms an adhesion complex [E-cadherin-p-catenin (or y-catenin)-cc-catenin] (Cadherin-Catenin-Complex, CCC), this complex play an important role in maintaining epithelial cell adhesion.Some catenins such as -, - and p120ctn catenins are also crucial in cell signaling, they play an important role in cell proliferation and cell apoptosis. Studies revealed that P-catenin dissociated from CCC and translocated into free catenin pool in cytosol after it has been phosphorylated at tyrosine or serine residues, and in this situation, the CCC has been disrupted and cell adhesion function disturbed. A large amount of the free p-catenins in the cytosol can be degraded by the tumor suppressor APC, and the remains translocate into nucleus and bind to transcriptional factor Tcf/Lef in the nucleus and then promote cell proliferation related gene or anti-apoptosis gene transcription.Changes in P-catenin expression or localization were found in cancer cells and tumor tissues, it had been reported that P-catenin translocated from membrane at the normal condition into the cytosol or nucleus in cancer cells. Recently, p-catenin has been referred to an oncogene.P120ctn is a more newly found catenin, studies revealed that it is also an important molecule in E-cadherin mediated cell-cell adhesion, and phosphorylated tyrosine in p120ctn were evidenced. Translocation of p120ctn occurred in cancer cells and tissues. Evidences showed that there were a key relationship between p120ctn translocation and tumoregenesis. Unfortunately, the down stream partner of p120ctn is not yet clear up today, and the role of nucleus translocated p120ctn in cell signaling is either not yet clear.There is a relationship between catenin phosphorylation, translocation and tumoregenesis, further more, in this relationship, cell signaling cascade and mitogen and their receptors are involved. Base on these evidences, people are trying to disturb the key molecules in this signaling cascade for anti-tumor purpose.We have identified p120ctn expression in cultured hepatocyte and liver tissues using RT-PCR, immunohistochemistry and immunofluorescence microscopy, p120ctnisoform 1A and 3 A expression have been detected in the cells and tissues. Also we found that p120ctn expressed mainly at cell membrane at cell-cell contact region in LO2 imortal human liver cells, while the molecule expressed mainly in cytoplasm and in nucleus in BEL-7404 human liver cancer cells, membrane expression reduced or disappeared in these cells. The molecule expressed at membrane, no immunoreaction was detected in cytoplasm or in nucleus in normal liver tissues. While in hepatocirrhosis tissues, the molecule expressed both at membrane and in cytosol, and the membrane expression increased, it suggested a compensative mechanism. P120ctn weakly expressed or disappeared at membrane in hepatocellular carcinoma tissues, immunoreaction were detected in cytosol and nucleus, it suggested that the molecule had translocated and cells lost adhesion abilities had malfunction in signaling, also P-catenin had similar changes as P120ctn.We also found that p1206"1 can be easily phosphorylated at tyrosine by epidermal growth factor (EGF). Tyrosine phosphorylation of p!20ctn strengthened BEL-7404 cells malignant behavior, and p120ctn translocated into nucleus. P-catenin had similar changes as p120ctn. Cells become thin and long and irregular in morphology after phosphorylation of p120ctn, but this situation was improved after cells transfected exogenous p120ctn isoform 3A, but it became worse while transfacted plus EGF stimulation for p120ctn abundantly translocated into nucleus, cell behavior became more invasive. Interestingly, we found P-catenin nucleus expression reduced and 'returned' to cytoplasm and membrane in some...