The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by α-T-catenin upregulation

By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of the pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell–cell adhesion protein α-T-catenin (CTNNA3). This is effectuated at the crucial epithelial–...

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Bibliographic Details
Published in:Human molecular genetics 2010-07, Vol.19 (13), p.2658-2667
Main Authors: van Dijk, Marie, van Bezu, Jan, van Abel, Daan, Dunk, Caroline, Blankenstein, Marinus A., Oudejans, Cees B.M., Lye, Stephen J.
Format: Article
Language:English
Subjects:
Alleles
alpha Catenin - metabolism
Biological and medical sciences
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Adhesion - genetics
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Diseases of mother, fetus and pregnancy
Female
Forkhead Transcription Factors - metabolism
Fundamental and applied biological sciences. Psychology
Genetic Association Studies
Genetics of eukaryotes. Biological and molecular evolution
Gynecology. Andrology. Obstetrics
Humans
Medical sciences
Molecular and cellular biology
Pre-Eclampsia - genetics
Pre-Eclampsia - metabolism
Pre-Eclampsia - pathology
Pregnancy
Pregnancy. Fetus. Placenta
Proto-Oncogene Proteins c-akt - metabolism
Trophoblasts - metabolism
Trophoblasts - pathology
Up-Regulation
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Summary:By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of the pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell–cell adhesion protein α-T-catenin (CTNNA3). This is effectuated at the crucial epithelial–mesenchymal transition of proliferative into invasive extravillous trophoblast. This STOX1–CTNNA3 interaction is direct and includes Akt-mediated phosphorylated control of nucleo-cytoplasmic shuttling and ubiquitin-mediated degradation as shared with the FOX multigene family. This, to our knowledge, is the first time a genotype associated with pre-eclampsia has been shown to directly limit first trimester extravillous trophoblast invasion, the earliest hallmark of pre-eclampsia.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/ddq152