Signalling pathways regulating the invasive differentiation of human trophoblasts: a review.
The invasive differentiation pathway of trophoblasts is an indispensable physiological process of early human placental development. Formation of anchoring villi, proliferation of cell columns and invasion of extravillous cytotrophoblasts into maternal decidual stroma and vessels induce vascular changes ensuring an adequate blood supply to the growing fetus. Extravillous trophoblast differentiation is regulated by numerous growth factors as well as by extracellular matrix proteins and adhesion molecules expressed at the fetal-maternal interface. These regulatory molecules control cell invasion by modulating activities of matrix-degrading protease systems and ECM adhesion. The differentiation process involves numerous signalling cascades/proteins such as the GTPases RhoA, the protein kinases ROCK, ERK1, ERK2, FAK, PI3K, Akt/protein kinase B and mTOR as well as TGF-beta-dependent SMAD factors. While an increasing number of signalling pathways regulating trophoblast differentiation are being unravelled, downstream effectors such as executing transcription factors remain largely elusive. Here, we summarise our current knowledge on signal transduction cascades regulating invasive trophoblast differentiation. We will focus on cell model systems which are used to study the particular differentiation process and discuss signalling pathways which regulate trophoblast proliferation and motility.
Pollheimer
J
J
Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Knöfler
M
M
D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases
D004268:DNA-Binding Proteins; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D051785:Smad Proteins; D015534:Trans-Activators; D020741:rho GTP-Binding Proteins; D054460:rho-Associated Kinases; C496050:PTK2 protein, human