PMC:4385186 / 32905-34526 JSONTXT

{"project":"2_test","denotations":[{"id":"25839328-22364861-2052603","span":{"begin":803,"end":805},"obj":"22364861"}],"text":"We next used the immunohistochemical method to determine whether a correlation exists between these genetic changes and the amount of ZNF750. As expected, ZNF750, a nuclear factor, was strongly stained in the nuclei of normal esophageal epithelial cells. Surprisingly, though, it was dramatically upregulated in the cytoplasm of ESCC tumor cells in comparison to that of normal tissue cells. Moreover, individuals with tumors harboring ZNF750 mutations had higher cytoplasmic expression levels than did those lacking ZNF750 mutations (Figure 5A). Mislocalization of a truncated (p.Ser70∗) ZNF750 (Figure 5B) indicated that cytoplasm translocation was partly caused by loss of the C-terminal nuclear localization sequence. ZNF750 regulates the gene program controlling terminal epidermal differentiation.43 For investigating a function for ZNF750 in tumorigenesis, shRNA-mediated stable ZNF750 depletion was followed by transfection with wild-type or altered (p.Ser70∗ or p.Trp207∗) ZNF750 in KYSE150 and KYSE140 cells. ZNF750 knockdown strongly promoted KYSE150 and KYSE140 cell proliferation, migration, and invasion. Moreover, functional studies demonstrated that wild-type ZNF750 inhibited cell growth, migration, and invasion, and this effect was abrogated by altered (p.Ser70∗ or p.Trp207∗) ZNF750 (Figure 5C; Figures S9D and S9E). Finally, ZNF750 depletion and p.Ser70∗ ZNF750 markedly increased tumor size in the xenograft system in mice, whereas wild-type ZNF750 significantly decreased it (Figure 5D). Our genetic observations and functional data therefore suggest that ZNF750 acts as a tumor suppressor in ESCC."}