Integrated in silico and in vitro analyses reveal E-cadherin crosstalk and TF: FVIIa complex-mediated trophoblast motility via MEK/JNK activation
Paper Details
Integrated in silico and in vitro analyses reveal E-cadherin crosstalk and TF: FVIIa complex-mediated trophoblast motility via MEK/JNK activation
Abstract
Tissue Factor (TF) is traditionally viewed as a coagulation initiator but increasingly recognized for extra hemostatic functions in cell signaling and migration. In trophoblasts, the TF:FVIIa complex may act as a critical regulator of cell motility during placental development. Yet how TF:FVIIa complex functions to drive human trophoblast migration remains poorly understood. This study investigated whether the TF:FVIIa complex promotes trophoblast migration through MAPK signaling using bioinformatics and functional assays. Genomic analysis of The Cancer Genome Atlas (TCGA) datasets from 657 gynecological samples revealed a significant positive correlation between TF (F3) and E-cadherin (CDH1) expression across three cohorts (R = 0.21–0.48, p < 0.05), supporting a partial epithelial-mesenchymal transition model for invasive cells. Protein-protein interaction networks identified MEK and JNK as central intermediates linking TF: FVIIa signaling to adhesion regulation. Functionally, FVIIa stimulation of HTR-8/SVneo trophoblasts induced dose-dependent migration increases (1.90-fold at 4 nM, p < 0.01). Inhibition of either MEK (U0126) or JNK (SP600125) completely blocked FVIIa-induced migration, demonstrating that both pathways are required for TF-driven migration. These findings establish TF: FVIIa as a key regulator of trophoblast migration through coordinated MEK/JNK activation, with implications for understanding defects in placental invasion and designing targeted interventions for pregnancy-related disorders.
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Kirthika Manoharan, Jagadish Krishnan, Vijaya Anand Arumugam, Shenbagam Madhavan*, 2025. Integrated in silico and in vitro analyses reveal E-cadherin crosstalk and TF: FVIIa complex-mediated trophoblast motility via MEK/JNK activation. Int. J. Biosci., 27(6), 136-144.
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