Glucose starvation induces fumarate hydratase succinylation and inhibits ferroptosis to maintain colon cancer cell proliferation - PubMed
4 hours ago
- #Ferroptosis
- #Colon Cancer
- #Succinylation
- FH downregulation in colorectal cancer (CRC) acts as a tumor suppressor.
- Glucose starvation reduces FH expression, accumulating fumarate and succinate, linked to poor prognosis.
- Accumulated fumarate stabilizes NRF2, upregulates GPX4 and FTH1 to inhibit ferroptosis and sustain proliferation.
- Glucose starvation induces CPT1A-mediated succinylation of FH at K66/K80, reducing its stability and promoting degradation via autophagy-lysosome pathway.
- The study reveals FH succinylation's role in CRC adaptation to glucose starvation, inhibiting ferroptosis to maintain proliferation.