The expression of "nuclear Met was investigated in both human HCC cell lines and tissue samples from the same patient. It has been demonstrated that nuclear Met is over expressed in HCC tumorous tissues compared to the comparable non-tumorous tissues. Furthermore, it was shown to be expressed more often along the course of HCC development, from non-tumorous liver through cirrhotic liver to early and advanced HCC. Furthermore, increased Met over expression in the nucleus was found to be linked with venous invasion and a shorter overall survival in HCC patients. We then confirmed that nuclear Met, which has a size of approximately 48 kDa and is composed solely of the cytoplasmic fragment of full-length Met, by demonstrating that it could only be detected by a Met antibody directed against the cytoplasmic domain of Met and not the extracellular domain of the protein. Later cellular fractionation and immune fluorescence microscopy revealed that this 48 kDa fragment of Met was present in the nucleus and that it was not dependent on the presence of a ligand for its presence. In addition, we discovered that a region before the tyrosine kinase domain following the juxta membrane region (P1027-L1157) is required for the translocation of nuclear Met to the nucleus. It was necessary to create nuclear Met over expressing stable clones in order to functionally describe the nuclear Met in HCC. These stable clones were subjected to a variety of functional investigations. We have established that nuclear Met has a proliferative effect on in vitro cell proliferation, anchorage independent growth, motility, and invasiveness in a number of experiments. Furthermore, over expression of Met in the nucleus of HCC cells increased the tumorigenicity of the cells in vivo. Our findings provided the first convincing evidence of a tumorigenic role for nuclear Met in HCC, and" they were published in Cancer Research.