TITLE: “Metabolic Reprogramming during Epithelial Crowding Underlies Jamming Transition”
ABSTRACT: Jamming, crucial for maintaining tissue integrity during morphogenesis and wound healing, becomes dysregulated in carcinoma metastasis and asthma. Despite its pathological significance, the molecular mechanisms governing jamming remain poorly understood. In this study, we utilized time-course transcriptome analysis and isotopologue metabolomics to elucidate the metabolic changes associated with jamming. Our findings reveal an energy-independent increase in glucose oxidation during cell jamming. We further demonstrated that reverting this metabolic shift by inhibiting the mitochondrial pyruvate carrier leads to upregulation of cell motility, effectively abolishing the jamming transition. This metabolically induced tissue fluidization is characterized by uncoordinated cell movements with enriched Rac/RhoA activity, in contrast to the collective migration observed in previous unjamming experiments. Additionally, we show that the preserved E-cadherin junction facilitates motility-driven elongation of cells. The identification of this metabolic regulation of jamming transition holds significant implications for understanding cancer dissemination and embryonic morphogenesis, both of which involve substantial metabolic reprogramming.
