Affordable Access

Publisher Website

Ubiquitin Ligase Cullin 7 Induces Epithelial-Mesenchymal Transition in Human Choriocarcinoma Cells*

Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Publication Date
DOI: 10.1074/jbc.m109.004200
  • Cell Biology
  • Developmental Biology


Germ line mutations of the ubiquitin ligase cullin 7 (CUL7) are linked to 3-M syndrome and Yakuts short stature syndrome, both of which are characterized by pre- and post-natal growth retardation. CUL7 knock-out mice show placental and embryonic defects similar to intrauterine growth retardation, suggesting a role of CUL7 in placentation. CUL7 was found in this study to be 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, 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 that the CUL7 E3 ligase is a key regulator in trophoblast cell epithelial-mesenchymal transition and placental development.

There are no comments yet on this publication. Be the first to share your thoughts.


Seen <100 times

More articles like this

Ubiquitin ligase cullin 7 induces epithelial-mesen...

on Journal of Biological Chemistr... Apr 02, 2010

The cullin7 E3 ubiquitin ligase: a novel player in...

on Cell cycle (Georgetown, Tex.) October 2008

PTEN loss induces epithelial--mesenchymal transiti...

on Anticancer Research November 2009

Chemoresistance to 5-fluorouracil induces epitheli...

on Biochemical and Biophysical Re... Jan 13, 2012
More articles like this..