Study On The Relationship Between Palmitate Acylate Membrane Protein 3 (MPP3) And The Occurrence And Metastasis

Tissue development, differentiation, and physiology require specialized cellular adhesion and signal transduction at sites of cell-cell contact. Scaffolding proteins that tether adhesion molecules, receptors, and intracellular signaling enzymes organize macromolecular protein complexes at cellular junctions to integrate these functions. One family of such scaffolding proteins is the large group of membrane associated guanylate kinases (MAGUKs). Genetic studies have highlighted critical roles for MAGUK proteins in the development and physiology of numerous tissues from a variety of metazoan organisms. In recent years, some evidence emerging to demonstrate that some members of the MAGUK are involved in progression of tumors, However, current knowledge of MAGUKs in cancer research is still very limited. As little knowledge of MPP3(membrane palmitoylated protein 3) in human hepatocellular carcinoma (HCC) has been reported before, exploration of the expression pattern as well as the physiological function of MPP3 in HCC would contribute to our comprehensive understanding of HCC progression.The mRNA expression of MPP3 were detected in 100 pairs of HCC tissue samples by real-time quantitative PCR taqman method and MPP3 mRNA was significantly higher in HCC than those in their adjacent nontumorous tissues. Overexpression of MPP3 was found to correlate significantly with history of suffering from hepatitis, tumor diameter greater than 5cm, less than 1,000 days of survival time by pathological correlation analysis. Both mRNA and protein levels of MPP3 were detected in 30 groups of HCC, portal vein tumor thromb and their adjacent nontumorous tissues and the up-regulated expression of MPP3 in portal vein tumor thromb was both significant compared with adjacent nontumorous tissue or HCC.The expression level of MPP3 in high metastatic hepatoma cell line MHCC-97H was also higher than low metastatic hepatoma cell line MHCC-97L, these data suggest that MPP3 maybe correlate with HCC metastasis.This assumption has been confirmed by cell migration and invasion assay in vitro, we constructed the stable expression of MPP3 in SMMC-7721 cell line and found that overexpression of MPP3 greatly enhance cell migration and invasion of SMMC-7721 cell line in vitro, and stable knockdown of MPP3 in MHCC-97H and Hep3B cell lines suppress cell migration and invasion, however overexpression or knockdown of MPP3 did not affect the rate of cell growth. In addition,we have done a preliminary study on the effect of MPP3 on HCC cell sensitivity to antineoplastic agents and detected resistance of stable knockdown of MPP3 in MHCC-97H and the control cell lines to 10 kinds of antineoplastic agents. As a result, we found knockdown MPP3 can increase MHCC-97H sensitivity to doxorubicin and daunorubicin.In summary, we found a gene MPP3 up regulated in HCC significantly, demonstrated MPP3 could promote HCC cell migration and invasion, demonstrated overexpression of MPP3 was associated with poor prognosis in HCC, and provided a new theoretical basis for HCC treatment.