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Article Abstract
The placenta serves as a vital interface for fetal-maternal exchange, relying on trophoblast differentiation for development. This process involves cytotrophoblasts (CTBs) transitioning into syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs), driving placental maturation. Focal adhesion kinase (FAK), a key cytoplasmic tyrosine kinase, regulates cellular processes such as proliferation, survival, and signaling. However, its role in trophoblast differentiation and metabolism remains unclear. Here, using human trophoblast stem cells (hTSCs) and trophoblast cell lines (BeWo, HTR8/SVneo), we investigated FAK signaling in trophoblast lineage differentiation. Inhibiting the FAK signaling pathway suppresses MAPK pathway activity, reduces glycolytic metabolism and impairs trophoblast syncytialization. Additionally, blocking FAK with the inhibitor Defactinib disrupts EVTs cytoskeleton and impairs migration, invasion, and differentiation potential. Notably, reduced FAK signaling is observed in patients with recurrent spontaneous abortion (RSA), suggesting a role in RSA pathogenesis. Our findings highlight FAK as a pivotal regulator of trophoblast lineage development, linking it to placental function and RSA. This study offers new insights into placental disorders and potential therapeutic targets.
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| http://dx.doi.org/10.1016/j.cellsig.2025.111946 | DOI Listing |
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