c-Fos-driven metabolic switch of α-ketoglutarate orchestrates progression in prostate cancer - PubMed
4 hours ago
- #metabolism
- #c-Fos
- #prostate cancer
- Prostate cancer exhibits heterogeneity with unique metabolic profiles, including a compensatory shift in α-ketoglutarate (α-KG) metabolism involving IDH1.
- IDH1 inhibition reduces α-KG levels, stabilizing HIF-1α and upregulating c-Fos, which enhances GLUD1 transcription to convert glutamate to α-KG.
- c-Fos upregulates FOXC1 and SOX2, driving neuroendocrine differentiation in prostate cancer.
- Targeting α-KG-metabolizing enzymes like IDH1 or GLUD1 inhibits tumor proliferation and induces oxidative stress, sensitizing tumors to ferroptosis.
- The study highlights c-Fos's role in metabolic adaptation and suggests new therapeutic strategies for prostate cancer treatment.