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The FOS transcription factor family differentially controls trophoblast migration and invasion.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2014 Feb 21; Vol. 289 (8), pp. 5025-39. Date of Electronic Publication: 2013 Dec 30. - Publication Year :
- 2014
-
Abstract
- Extravillous trophoblast invasion is a fundamental component of human placentation. Invading trophoblast cells promote blood flow to the conceptus by actively remodeling the uterine vasculature. The extent of trophoblast invasion is tightly regulated; aberrant invasion is linked with several obstetrical complications. However, the transcriptional networks responsible for controlling the extent of trophoblast invasion are not well defined. Previous studies have identified high levels of FOS (FOS, FOSB, FOS-like (FOSL) 1, and FOSL2) proteins in extravillous trophoblast cells. These proteins form part of the activating protein-1 (AP-1) transcription factor complex and are implicated in regulating gene networks controlling cellular invasion in diverse biological systems. Therefore, we hypothesized that FOS family proteins play a role in regulating trophoblast invasion. We assessed expression of FOS family proteins in trophoblast cell lines and human placentae at different gestational ages. FOS, FOSB, and FOSL1 proteins were robustly increased in trophoblast cells subject to wound-based migration assays as well as Matrigel-based invasion assays. FOS knockdown resulted in cessation of proliferation and an induction of migration and invasion concomitant with robust expression of matrix metalloproteinase (MMP) 1, MMP3, and MMP10. Conversely, FOSL1 knockdown abrogated trophoblast migration and invasion and inhibited the production of MMP1, MMP3, and MMP10. In human placenta, FOS was expressed in proximal anchoring villi in conjunction with phospho-ERK. FOSL1 was temporally expressed only in the distal-most extravillous trophoblast cells, which represent a migratory cell population. Therefore, FOS and FOSL1 exert opposing effects on trophoblast invasion.
- Subjects :
- Cell Cycle genetics
Cell Line
Cell Proliferation drug effects
Collagen pharmacology
Drug Combinations
Extracellular Signal-Regulated MAP Kinases metabolism
Female
Gene Expression Regulation drug effects
Gene Knockdown Techniques
Humans
Laminin pharmacology
MAP Kinase Signaling System drug effects
Matrix Metalloproteinases metabolism
Neovascularization, Physiologic drug effects
Pregnancy
Proteoglycans pharmacology
Proto-Oncogene Proteins c-fos genetics
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Small Interfering metabolism
Trophoblasts drug effects
Trophoblasts enzymology
Cell Movement drug effects
Multigene Family
Proto-Oncogene Proteins c-fos metabolism
Trophoblasts cytology
Trophoblasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 289
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24379408
- Full Text :
- https://doi.org/10.1074/jbc.M113.523746