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Members of the L6 family of membrane proteins, a branch of the tetraspanin superfamily, are overexpressed in tumor cells from many types of cancers. However, direct evidence of their oncogenic activity has not been previously shown. In this issue of the JCI, Lee et al. demonstrate that overexpression of the tetraspanin superfamily member TM4SF5 in human hepatocellular carcinoma cells causes cellular phenotypic changes that resemble classical descriptions of epithelial-mesenchymal transition (EMT), with some unique aspects (see the related article beginning on page 1354). They also show that these TM4SF5-mediated effects trigger tumor formation when these cells are injected into mice. The study implicates TM4SF5, for the first time to our knowledge, in EMT oncogenic pathways of cancer progression.

Original publication




Journal article


J Clin Invest

Publication Date





1347 - 1350


Animals, Carcinoma, Hepatocellular, Cell Differentiation, Epithelial Cells, Humans, Membrane Proteins, Mesoderm, Mice, Models, Biological