Activation of the WNT4/ ?-catenin/FOXO1 pathway by PDK1 promotes cervical cancer metastasis and EMT process.

This study aimed to elucidate the role of pyruvate dehydrogenase kinase-1 (PDK1) in cervical cancer (CC) by investigating its impact on cell proliferation, migration, and epithelial-mesenchymal transition (EMT) under hypoxic conditions.PDK1-silenced CC cell lines were established using lentiviral shRNA technology. Cell migration and invasion were assessed through scratch and Transwell ...
assays, respectively. Cellular activity and apoptosis-related protein expression levels were evaluated using MTT assays and western blotting. Transcriptome sequencing elucidates the regulatory pathways impacted by PDK1 silencing, and rescue experiments confirmed the underlying mechanisms. Xenograft models with nude mice were used to validate the effects of PDK1 silencing on CC progression.PDK1 silencing reduced migration, invasion, and cellular activity under hypoxic conditions while promoting apoptosis. Transcriptomic analysis revealed that PDK1 suppression downregulated the WNT4/?-catenin/FOXO1 pathway, decreasing EMT-related protein expression. Mechanistically, PDK1 enhanced ?-catenin stability by inhibiting its phosphorylation through AKT-mediated GSK3? inactivation, promoting EMT and anti-apoptotic gene transcription.Targeting PDK1 may provide novel therapeutic strategies specifically for CC by modulating the WNT4/?-catenin/FOXO1 pathway and associated EMT and apoptotic processes.
Mesh Terms:
Animals, Apoptosis, Cell Line, Tumor, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Female, Forkhead Box Protein O1, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Nude, Neoplasm Metastasis, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Signal Transduction, Uterine Cervical Neoplasms, Wnt Signaling Pathway, beta Catenin
J Mol Histol
Date: Jan. 09, 2025
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