Germline mutations of cullin 7 (CUL7), a scaffold protein for the RING type E3 ligases, are linked to 3-M syndrome and Yakuts short stature syndrome, both of which are characterized by pre- and post-natal growth retardation. CUL7 knockout mice show placental and embryonic defects similar to intrauterine growth retardation, suggesting a role of CUL7 in placentation.
A recent study from Dr. Hongmei Wang’s team found CUL7 was highly expressed in first trimester invasive human placental villi, as well as in HTR8/SVneo and B6Tert cells, two cell lines derived from human first trimester trophoblast cells. However, CUL7 levels in term trophoblast cells or JEG-3 cells, which are derived from human choriocarcinoma but exhibit weak invasion capacity, were low or undetectable. Forced expression of CUL7 in JEG-3 cells induced cell morphological changes characteristic of epithelial-mesenchymal transition (EMT), which was accompanied by a complete loss of the epithelial markers E-cadherin and P-cadherin, and a significant elevation of mesenchymal markers Vimentin and N-cadherin. JEG-3 cells expressing CUL7 exhibited enhanced cell migration and invasion. Conversely, CUL7-specific RNA interference in HTR8/SVneo cells resulted in increased E-cadherin expression and reduced cell migration and invasion. Furthermore, CUL7 expression down-regulated E-cadherin mRNA expression by up-regulating ZEB1 and Slug, two transcriptional repressors of E-cadherin. Finally, CUL7-induced loss of E-cadherin expression was partially reversed by treatment of CUL7-expressing cells with the proteasome inhibitor MG-132. These results suggest a novel function of CUL7 E3 ligase as an inducer of EMT.
JJ Fu*, XY Lv*, HY Lin, L Wu, R Wang, Z Zhou, BH Zhang, YL Wang, BK Tsang, C Zhu, and HM Wang. Ubiquitin ligase cullin 7 induces epithelial-mesenchymal transition in human choriocarcinoma cells. J Biol Chem 2010 Feb 5 [Epub ahead of print] (*, equal contribution)
The 5th International Conference on Rodent Biol...
