Targeting glypican-3 as a new frontier in liver cancer therapy

Figure 4 Glypican-3-mediated regulation of c-Myc stability and metabolic adaptation under hypoxia. Glypican-3 (GPC3) regulates tumor metabolic adaptation and stemness by modulating c-Myc protein stability under normoxic and hypoxic conditions. Under normoxic conditions, c-Myc is more prone to ubiquitination and degradation when GPC3 expression is low. Under hypoxia, GPC3 is upregulated and promotes global protein lactylation, which specifically prevents c-Myc degradation, thereby stabilizing c-Myc protein and enhancing glycolysis and stemness. GPC3: Glypican-3.