A study published in Communications Biology has identified pyruvate carboxylase (PC) as a key driver of metabolic changes in epithelial ovarian cancer. Researchers found that high PC levels are linked to more advanced disease, metastasis, recurrence, and poorer survival.
The study shows that PC helps cancer cells build up fats by boosting the production of triglycerides and fatty acids, mainly by increasing new fat synthesis rather than fat uptake or breakdown. It does this through a linked metabolic and epigenetic system involving TET1 and SREBP1a, which activates genes responsible for lipid production.
Mechanistically, PC raises acetyl-CoA levels, which stabilizes the SREBP1a protein and prevents its breakdown. It also increases alpha-ketoglutarate, which enhances TET1 activity and changes DNA marks in genes involved in fat synthesis, making them more active.
Researchers tested a combination therapy targeting this pathway using inhibitors of PC, TET1, and SREBP1. The triple combination strongly reduced fat production and tumor growth in lab and animal models, with no major toxicity observed.
The findings suggest that blocking this PC–TET1–SREBP1a pathway could be a promising treatment strategy for aggressive ovarian cancer that depends heavily on lipid metabolism.