Glycolysis regulates palatal mesenchyme proliferation through Pten-Glut1 axis via Pten classical and non-classical pathways

Abnormal embryonic development can result in cleft palate (CP), a condition that is difficult to detect through genetic screening and requires long-term treatment from infancy to adulthood. Currently, no preventive therapies are available for CP. Germline deletion of the phosphatase and tensin homolog (Pten) gene has been linked to embryonic malformations and is known to regulate tumor cell proliferation via glycolysis. However, the role of Pten in CP, and its connection to glycolysis, remains unclear. In this study, we established both in vitro and in vivo Pten knockdown models. Our findings provide preliminary evidence that inhibiting Pten—using agents such as VO-OHpic—may offer a potential early intervention strategy during critical stages of palate development, particularly in cases where the pregnant mother is exposed to harmful environmental factors. This protective effect may be mediated by the interplay between Pten signaling and glycolytic pathways.