Isoleucine and Valine Drive Prostate Cancer via 70% Propionyl-CoA Supply and Cholesterol Signaling
Updated
Updated · Nature.com · Aug 20
Isoleucine and Valine Drive Prostate Cancer via 70% Propionyl-CoA Supply and Cholesterol Signaling
3 articles · Updated · Nature.com · Aug 20
Summary
About 70% of prostate cancer cells’ propionyl-CoA pool came from isoleucine and valine, the study found, linking those amino acids directly to faster tumor growth, lung colonization and resistance to androgen deprivation.
Propionyl-CoA acted as a signal rather than just a fuel source: it propionylated and stabilized nuclear SREBP2, boosting cholesterol biosynthesis, de novo androgen production and androgen receptor signaling even under therapeutic stress.
In mice, cutting dietary isoleucine and valine to 25% of standard levels lowered serum and tumor propionylcarnitine, suppressed xenograft growth and reduced metastatic colonization; adding propionylcarnitine partly rescued growth in cell models.
Blocking downstream cholesterol or steroid synthesis with mevastatin or CYP11A1 inhibition blunted the growth effects, pointing to the propionyl-CoA-SREBP2-androgen axis as a potential treatment target in castration-resistant prostate cancer.