Work

Hexokinase 2-driven aerobic glycolysis modulates YAP1 in placental trophoblast development

Year: 2025

Type: article

Abstract: Recurrent pregnancy loss (RPL) is a severe complication, and its risk is heightened by dysregulated trophoblast development. However, the underlying mechanisms remain unclear. Herein, we show that a portion of villous samples from patients with RPL display reduced hexokinase II (HK2) and Yes-associated protein 1 (YAP1) expression compared with healthy controls. Moreover, in human trophoblast stem (TS) cell models, blocking HK2 activities via exposure to 3-bromopyruvate markedly reduced cell proliferation and induced cell cycle arrest by regulating YAP1 phosphorylation and localization. This was partially reversed by the YAP signaling activator TT-10. Moreover, YAP1 contributes to aerobic glycolysis regulation by influencing HK2 activity. Together, these findings demonstrate an interplay between the Hippo/YAP1 pathway and glucose metabolism in placental trophoblast development and highlight an approach for RPL intervention. • HK2-driven aerobic glycolysis associated with RPL onset. • HK2 inhibition effects Hippo/YAP pathway activation • YAP1 regulates HK2 activity forming a feedback loop with glucose metabolism • YAP signaling activator, TT-10 maybe the potential therapeutic agent for treating RPL

Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI: 10.1016/j.bbadis.2025.167872